493

Chapter 6

Interventions for Smoking Cessation and Treatments 

for Nicotine Dependence

Introduction 495

Literature Review Methods 496

Behavioral and Psychological Treatments 496

Treatment Strategies 497

Behavioral Therapy 497

Cognitive Therapy 497

Motivational Interviewing 498

Acceptance and Commitment Therapy 499

Contingency Management and Monetary Incentives 499

Relapse Prevention and Recovery 500

Intervention Delivery Modalities 501

Self-Help Materials 501

Face-to-Face Counseling 501

Technology-Mediated Delivery Approaches 504

Pharmacologic Treatments 509

Nicotine Replacement Therapy 515

Bupropion 516

Varenicline 516

Additional Approaches to Medication Therapy 517

Combination Pharmacotherapy 517

Pre-Loading Medication 518

Gradual Reduction 518

Extended Treatment 519

Precision Medicine 519

Real-World Effectiveness of Cessation Medications 520

Combination Treatment—Behavioral Therapy and Pharmacotherapy 522

Modified and Alternative Tobacco Products 522

Very-Low-Nicotine-Content Cigarettes 522

E-Cigarettes 524

Teachable Moments 532

Hospitalization 532

Surgery 534

Lung Cancer Screening 535

Readiness to Quit and Approaches for Quitting Ambivalence 536

Considerations for Subpopulations 537

Pregnant Women 537

Lesbian, Gay, Bisexual, and Transgender Populations 538
494

Populations with Mental Health Conditions and Co-Occurring Substance Use Disorders 539

Adolescents 540

Dual Tobacco Product Users 541

Light and Nondaily Tobacco Users 543

Emerging Intervention Approaches 544

Emerging Behavioral Treatments 544

Expanding Behavioral Treatment Targets 544

Use of Emerging Technology 544

Emerging Pharmacologic Approaches 545

Summary of the Evidence 546

Conclusions 547

References 549
Interventions for Smoking Cessation and Treatments for Nicotine Dependence 495

Smoking Cessation

Introduction

There are now more former cigarette smokers than 

current smokers in the United States (U.S. Department of 

Health and Human Services [USDHHS] 2014). For more 

than a decade, national surveillance data on smoking 

cessation have revealed a similar pattern, with modest 

improvement—two-thirds of adult cigarette smokers indicate a desire to quit, and just over half try to quit each year; 

however, less than 10% of smokers who try to quit succeed in quitting for 6 months or longer (Babb et al. 2017). 

A large body of evidence highlights the efficacy of multiple treatments that can double or triple the rate of success in quitting smoking (Fiore et al. 2008; Prochaska and 

Benowitz 2016). This chapter reviews both evidence-based 

and emerging potential treatments for smoking cessation.

Current evidence-based treatment approaches 

to smoking cessation include several behavioral treatments—such as individual, group, and telephone counseling—and seven pharmacotherapies approved by the 

U.S. Food and Drug Administration (FDA). These treatments have been shown to be effective when delivered 

across a wide variety of settings, via several platforms, and 

to a diversity of populations—including groups that have 

been disproportionately impacted by tobacco use, such 

as low-income populations, and populations with other 

comorbid medical conditions, including behavioral health 

conditions (U.S. Preventive Services Task Force [USPSTF] 

2015). Evidence indicates that the combined use of both 

behavioral interventions and pharmacotherapies produces the largest cessation effects (Fiore et al. 2008; Stead 

and Lancaster 2012a; Stead et al. 2015), but the evidence 

also indicates that several of these treatments are effective when used alone (Fiore et al. 2008; Cahill et al. 2013; 

USPSTF 2015; Lancaster and Stead 2017). 

The cost-effectiveness of smoking cessation has 

been documented extensively (Jha et  al. 2015) (see 

Chapter 5. The Benefits of Smoking Cessation on Overall 

Morbidity and Economic Costs). For example, Maciosek 

and colleagues (2017a,b) assessed the potential impact of 

28 evidence-based clinical preventive services in terms of 

their cost-effectiveness and clinically preventable burden 

(measured by quality-adjusted life-years [QALYs] saved). 

The assessment, which included clinical preventive services for a variety of different risk factors, found that two 

of the three highest ranking preventive services were 

related to tobacco, including (a)  tobacco use screening 

and a brief counseling intervention to encourage cessation among adults and (b) counseling to prevent initiation 

of tobacco use among youth.

Data indicate that despite the availability of evidencebased treatments to achieve smoking cessation, less than 

one-third of adult cigarette smokers who attempt to quit 

use any type of cessation counseling and/or FDA-approved 

cessation medication (Babb et  al. 2017). Furthermore, 

undertreatment is common among smokers who use cessation treatments; rates of relapse are high (above 50%) 

(García-Rodríguez et al. 2013); and most smokers attempt 

to quit without using treatment (i.e., they try to quit unassisted or “cold turkey”), with success rates of approximately 

7–8% (Fiore and Jaen 2008; Prochaska and Benowitz 

2016; Babb et  al. 2017; Caraballo et  al. 2017). Unaided 

quitting likely remains common for a number of reasons, 

including the frequent lack of health insurance among 

tobacco users (nearly 30% of adult cigarette smokers are 

uninsured [Jamal et al. 2018]); inadequate public and private insurance coverage of cessation treatments (DiGiulio 

et al. 2018); inadequate and cumbersome reimbursement 

for cessation treatments offered by clinicians and hospitals (Fiore et al. 2008); inadequate promotion of cessation 

treatments to smokers and healthcare providers, which 

can contribute to low use of these treatments (Fiore et al. 

2008); the widespread perception that quitting cold turkey 

is at least as effective as quitting with the help of counseling and/or medication (Fiore et al. 2008); underfunding 

of state tobacco quitlines and other cessation services 

(USDHHS 2014; Campaign for Tobacco-Free Kids 2018); 

and inadequate integration of tobacco use screening and 

cessation interventions into routine clinical care (Babb 

et al. 2017). In addition, because of a lack of specialized 

training about nicotine dependence and treatment, many 

clinicians report being hesitant to engage patients in conversations about cessation because they feel they lack the 

requisite knowledge to do so effectively (Zapka et al. 1999; 

Simoyan et al. 2002; Blumenthal 2007). 

In the past, the tobacco industry has spread the misconceptions that smoking is a personal choice or simply a 

bad habit, that quitting is a matter of willpower, and that 

addiction to nicotine is akin to being addicted to caffeine 

(Henningfield et al. 2006). These messages have contributed to most smokers trying to quit through sheer determination instead of combining a strong motivation to 

quit with the use of evidence-based cessation treatments. 

The reality is that nicotine is addictive, and smoking is 

not merely a habit (USDHHS 1988). Although habitual 

components of smoking reinforce use, nicotine is a highly 

addictive drug, like heroin and cocaine (USDHHS 1988, 

2014), and nicotine addiction is a chronic, relapsing 
A Report of the Surgeon General

496 Chapter 6

condition. Although a majority of smokers in the United 

States who quit successfully do so without assistance, 

smokers who use medication and/or behavioral support as 

part of a quit attempt substantially increase their chances 

of quitting (Fiore et al. 2008). The conceptualization of 

nicotine dependence as a chronic, relapsing condition is 

not new (Fiore et al. 2008), but it has led to reframing the 

delivery of smoking cessation treatment as “chronic disease management,” which in turn has given rise to more 

systematic approaches to delivering nicotine dependence 

treatment in healthcare settings (Steinberg et al. 2008; 

Foulds et al. 2010). 

Behavioral and Psychological Treatments

Notable discoveries in the behavioral and social sciences have broadened and deepened understanding of psychosocial influences on the nature and treatment of nicotine dependence, which has given rise to new approaches 

to behavioral treatment. It has become clear that, as acute 

nicotine withdrawal dissipates as the length of the quit 

attempt increases, several factors—including intermittent negative emotional states, repeated urges to smoke, 

diminished motivation, and decreased self-efficacy about 

quitting—can persist throughout the cessation process 

Literature Review Methods

This chapter reviews the evidence base for current 

and potential emerging treatments for smoking cessation, 

adding to research from the U.S. Public Health Service’s 

Clinical Practice Guideline on Treating Tobacco Use and 

Dependence: 2008 Update (hereafter referred to as the 

Clinical Practice Guideline) (Fiore et al. 2008). It also 

explores approaches to increase the impact of smoking cessation treatments through improved efficacy and increased 

reach. The impact of a smoking cessation intervention is a 

function of effectiveness (i.e., success as measured in sustained quit rates of, for example, greater than 6 months) 

multiplied by reach (i.e., the proportion of the population 

of smokers engaged in treatment). Importantly, interventions that increase reach (i.e., those that are more broadly 

available and accessible to people, have greater appeal, 

and are therefore more widely used) may sacrifice efficacy 

or intensity, while interventions that are more intensive 

and more effective may have limited reach (Glasgow et al. 

2011; Zhu et al. 2012). Given the reality of funding constraints, most states, healthcare systems, and other stakeholders do not have the option of maximizing both the 

effectiveness and reach of cessation treatments; in practice, they have to balance these approaches.

For this chapter, 38 Cochrane reviews were examined 

in early 2017. Additional literature searches of Englishlanguage articles in PubMed were used to identify new 

literature published since the original Cochrane reviews. 

Searches were primarily restricted to randomized controlled trials (RCTs) of smoking cessation interventions 

using the terms smoking cessation and randomized controlled trial. In areas where RCTs were not available, the 

chapter discusses the available science and identifies areas 

that lacked depth of evidence from RCTs. Consistent with 

previous Surgeon General’s reports on tobacco, the content 

in this report was revised throughout the review process to 

include studies and information not available at the time 

the chapters were initially drafted, most notably for topics in 

which the available science is rapidly emerging (e.g., electronic cigarettes [e-cigarettes]) (King et al. 2018a).

Data reviewed in this chapter are overwhelmingly 

drawn from studies of adult cigarette smoking cessation, 

as opposed to cessation of other forms of tobacco products 

(e.g., cigars, cigarillos, smokeless tobacco, hookah, and 

e-cigarettes). The paucity of research on cessation treatments for noncigarette tobacco products does not allow 

for a separate and comprehensive scientific evaluation of 

such treatments. 

This chapter is divided into seven sections: behavioral and psychological treatments, pharmacologic treatments, teachable moments, considerations for subpopulations, emerging intervention approaches, summary of the 

evidence, and conclusions. 

and undermine quitting (Liu et al. 2013; Ussher et al. 

2013). Furthermore, encountering environments and 

situations previously associated with smoking, such as 

going to establishments that serve alcohol or interacting 

with friends who smoke, has been shown to increase risk 

of relapse (Conklin et al. 2013). Intensive behavioral cessation treatment models for smokers with mental health 

conditions and substance use disorders that have been 

adapted to address these factors have been shown to 

improve quit rates (Das and Prochaska 2017). 
Interventions for Smoking Cessation and Treatments for Nicotine Dependence 497

Smoking Cessation

Behavioral and psychological strategies that have 

been shown to be effective in treating tobacco use and 

nicotine dependence include behavioral therapy and cognitive behavioral therapy (CBT) (Sykes and Marks 2001; 

Fiore et al. 2008; Perkins et al. 2008), motivational interviewing (Lindson-Hawley et  al. 2015), acceptance and 

commitment therapy (Bricker et  al. 2013), and contingency management or incentive-based interventions 

(which have been found to be effective while incentives 

are in place) (Cahill et  al. 2015). These strategies can 

be individual- or group-based and can vary in intensity 

(from brief to more intensive) and in the mode of delivery 

(e.g., delivery by a clinician, counselor, telephone, or computer). Most research on behavioral treatments has considered packages of multiple treatment elements instead 

of comparing one element with another (e.g., studies of 

treatment optimization), making a review of each treatment approach challenging (Piper et  al. 2016). In general, the data show a robust dose-response curve, with 

more intensive behavioral and psychological treatments 

(e.g.,  higher amounts of contact time, more sessions) 

yielding greater odds of sustained cessation (Fiore et al. 

2008; USPSTF 2015). 

Treatment Strategies

Behavioral Therapy

A large body of scientific literature supports the use 

of behavioral therapy to help people quit smoking (Fiore 

et al. 2008; Stead et al. 2016; Lancaster and Stead 2017). 

Such approaches can be delivered by various types of 

healthcare providers or counselors to individual persons 

or groups. Behavioral therapy, which is commonly used 

with smokers who are contemplating quitting or preparing 

to quit, seeks to address the historical learning processes 

directly relevant to smoking and the current contextual 

factors that make it difficult to quit (e.g., social, behavioral, and environmental factors) (Webb et al. 2010b). 

Available evidence supports the effectiveness of both 

brief cessation interventions and longer, more intensive 

interventions. USPSTF (2015) and the Clinical Practice 

Guideline (Fiore et al. 2008) each concluded that both 

minimal (<20 minutes in a single visit) and intensive 

(≥20 minutes plus one or more follow-up visits) interventions delivered by clinicians are effective in increasing the 

proportion of adults who successfully quit smoking and 

remain abstinent for at least 6 months, which is commonly referred to as recent successful cessation. USPSTF 

(2015) and the Clinical Practice Guideline (Fiore et al. 

2008) each also concluded that there is a dose-response 

relationship between the intensity of counseling and 

quitting success—that is, the greater the intensity of 

counseling, the higher the likelihood an individual will 

quit. Accordingly, behavioral therapy approaches for 

smoking cessation are delivered over several weeks and 

focus on the physiological, psychological, social, and environmental aspects of smoking and nicotine dependence 

(Fiore et al. 2008; USDHHS 2010, 2014). Group treatment typically occurs weekly for several weeks in a series 

of 60- to 90-minute sessions (Foulds et al. 2006; Kotsen 

et al. 2017). For example, Public Health England (2017) 

recommended weekly visits for 6–12 weeks for individuals (30–45  minutes per visit) and groups (60 minutes 

per visit). 

Behavioral treatment approaches equip smokers 

with practical strategies to avoid and/or cope with triggers, manage cravings, and reduce withdrawal symptoms (Center for Substance Abuse Treatment 2006). 

These interventions often cover a wide variety of topics—

including advice on quitting smoking; assessment of prior 

quit attempts and lessons that can be drawn from them; 

assessment of current motivation to quit; identification 

of cues and triggers for smoking and ways to avoid or 

manage them; tips on ways to manage mood; and promotion of adherence to treatment engagement (such as using 

medications correctly) and continued treatment engagement. Adherence to treatment engagement and continued 

treatment engagement can be promoted by addressing 

skill building; self-managing withdrawal symptoms; 

accepting social support; and managing such associated 

health issues as stress, moodiness, and other substance 

use (Fiore et al. 2008). 

Cognitive Therapy

Cognitive therapy, which includes CBT, is a psychotherapeutic approach rooted in the idea that behavioral problems can be maintained by cognitive factors, 

including beliefs that lead to automatic thoughts about 

particular situations. The model uses specific therapeutic strategies to target maladaptive cognitions and 

help change problematic behaviors (Ellis 1962; Beck 

1970; Butler et al. 2006). Contemporary applications 

of CBT typically emphasize cognitive factors and emotional, physiological, and behavioral components that 

can reinforce behavior (Butler et al. 2006; Hofmann et al. 

2013). CBT is among the most researched psychotherapeutic approaches (Hofmann et al. 2012), with studies 

addressing a wide variety of behavioral and cognitive disorders, including smoking cessation.

Treatments based on CBT techniques have been 

found to be highly effective in smoking cessation (Sykes 

and Marks 2001; Fiore et al. 2008; Perkins et al. 2008). In 

a systematic review of cognitive therapies from 21 RCTs 
A Report of the Surgeon General

498 Chapter 6

that were conducted with 4,946 participants since 2009, 

the Norwegian Institute of Public Health concluded that: 

• Cognitive therapies have similar effects to usual care 

or minimal interventions in terms of rates of smoking 

abstinence (up to 6–12 months; n = 3 studies);

• Cognitive therapies combined with nicotine replacement therapy (NRT) result in higher abstinence 

rates (up to 12 months) compared with other interventions that are combined with NRT (n = 8 studies); 

• Cognitive therapies result in a higher smoking abstinence rate (up to 12 months) compared with other 

interventions (e.g., advice to quit, exercise, health 

education) (n = 6 studies); and

• Cognitive therapies plus medications improve 

smoking abstinence rates (up to 12 months) compared with medication only (n = 5 studies) (Denison 

et al. 2017). 

CBT has also been studied in relation to other cessation treatments and was found in a meta-analysis by 

Garcia-Vera and Sanz (2006) to be superior, both alone 

and in combination with NRT, compared with NRT alone. 

Studies have also shown CBT to be effective for 

smoking cessation in specific populations. For example, 

in a sample of African Americans, Webb and colleagues 

(2010a) found that CBT at least doubled the likelihood 

of cessation through the 6-month follow-up compared 

with a control group that received only health education. 

In a separate study, Webb Hooper and colleagues (2017) 

found that culturally specific CBT resulted in double the 

7-day point-prevalence cessation rate compared with 

nonculturally specific CBT and was significantly more 

effective at 3-month follow up. CBT has been shown to 

increase cessation when combined with NRT or other cessation medication in populations who use tobacco and 

have comorbid substance use or mental health conditions (Haas et  al. 2004; Ziedonis et  al. 2008; Magill and 

Ray 2009). However, studies assessing the use of CBT in 

smokers with schizophrenia, either with or without other 

intervention components, have yielded more mixed findings (Gelkopf et  al. 2012; Tsoi et  al. 2013; Rüther et  al. 

2014; Brody et al. 2017). 

Recent research has focused on improving smoking 

cessation outcomes from previous CBT trials. For example, 

in a 2017 two-arm, parallel group RCT of a communitybased adult sample (n  =  219), extended CBT treatment 

of 48 weeks did not yield better cessation outcomes compared with 26  weeks of treatment (Laude et  al. 2017). 

Research has also focused on adapting CBT interventions 

to mobile health (mHealth) and web-based platforms and 

adding technology-based components to further enhance 

CBT, including testing the effectiveness of CBT in an appbased format (vs. a non-CBT app) (Tudor-Sfetea et al. 2018) 

and adding virtual reality to CBT to create an immersive 

and interactive cue exposure paradigm (e.g., exposure to 

smoking cues without reinforcement, with the goal of disassociating those cues) to standard treatment (Culbertson 

et al. 2012).

Motivational Interviewing

Both motivational interviewing and adaptations 

of this approach make use of a distinct style of counseling that is directive, patient-centered, nonconfrontational, nonjudgmental, and highly collaborative (Miller 

and Rollnick 2002). Motivational interviewing—which 

can be delivered by healthcare providers, counselors, or 

quitline coaches—aims to help people explore and resolve 

any ambivalence about making a behavior change, such 

as quitting smoking (Miller and Rollnick 2002; LindsonHawley et al. 2015). This technique is typically used with 

persons who are not yet ready to quit tobacco (Miller and 

Rollnick 2002; Fiore et al. 2008). Counseling techniques—

such as expressing empathy, actively listening, reflecting 

back on what one heard, and building self-efficacy—

are at the core of motivational interviewing (Miller and 

Rollnick 2002).

Motivational interviewing was initially developed to 

treat alcohol addiction (Miller 1983) and was subsequently 

adapted for use in tobacco cessation. Lindson-Hawley and 

colleagues (2015) reviewed 28 studies that compared motivational interviewing to brief advice or usual care for the 

treatment of tobacco use. Motivational interviewing was 

used in one to six sessions lasting from 10 to 60 minutes and 

was delivered by clinicians in primary care settings, emergency departments, or hospitals; in the community; via 

telephone quitlines; and in military settings. Motivational 

interviewing was found to significantly increase successful 

quitting compared to those not receiving the intervention 

(relative risk [RR]  =  1.26; 95% confidence interval [CI], 

1.16–1.36; 28  studies; N  =  16,803). Short motivational 

interviewing interventions (<20 minutes per session) had 

an RR of 1.69 (95% CI, 1.34–2.12; 9 trials; N = 3,651). Both 

single-session (RR  =  1.26; 95%  CI, 1.15–1.40; 16  trials; 

N = 12,103) and multiple-session (RR = 1.20; 95% CI, 1.02–

1.42; 11 trials; N = 3,928) treatments increased the likelihood of quitting compared with controls. In summary, 

motivational interviewing is an evidence-based approach 

that has been shown, when delivered by clinicians or 

trained counselors, to be more effective in increasing readiness to quit and in helping people quit smoking than brief 

advice or usual care (e.g.,  self-help materials) (LindsonHawley et al. 2015). 
Interventions for Smoking Cessation and Treatments for Nicotine Dependence 499

Smoking Cessation

Acceptance and Commitment Therapy

Acceptance-based therapies (ACTs) draw on cognitive therapies but focus on changing psychological events 

directly. Specifically, ACTs seek to change the function 

of those events and the relationship an individual has 

to them (Hayes 2004; Hayes et al. 2006). ACTs focus on 

the context and functions of psychological phenomena, 

emphasizing contextual and experiential change strategies to help individuals become more willing to experience 

their physical sensations, emotions, and thoughts (Hayes 

et  al. 1999; Hayes et  al. 2006). In ACTs, “acceptance” is 

rooted in accepting intense physical sensations (e.g., nicotine withdrawal or urges to smoke) and the emotions and 

thoughts that accompany those sensations (e.g., anger or 

sadness, thoughts about wanting a cigarette, etc.). In contrast, “commitment” focuses on articulating what is particularly important to or valued by an individual and leveraging those values to motivate and guide specific actions, 

like quitting smoking (Hayes et  al. 2001, 2006, 2013; 

Bricker et al. 2010). Clinical treatment research supports 

ACTs for general behavior change and condition management, including in populations diagnosed with such disorders as major depression, anxiety disorders, borderline 

personality disorder, chronic pain, and substance abuse 

(including tobacco use) (Khoury et al. 2013; Kelly et al. 

2015; Linehan et  al. 2015; Cristea et  al. 2017; Meyers 

et  al. 2017). With regard to smoking cessation, a quasiexperimental study (n = 81 adult smokers) by HernándezLópez and colleagues (2009) compared ACT with CBT 

using seven weekly 90-minute sessions in a group format. 

The 30-day point-prevalence quit rate at 12-month followup was 30.2% in the ACT condition and 13.2% in the CBT 

condition (odds ratio [OR] = 5.13, p <.02). A randomized 

trial of 302 adult smokers compared individual and group 

ACT therapy with bupropion to bupropion only (Bricker 

et  al. 2014a). In this study, intent-to-treat quit rates at 

12-month follow-up were 32% in the ACT arm versus 

18% in the bupropion-only arm (p  <.05). ACT has also 

been studied as part of a telephone-based intervention. 

For example, in a pilot randomized trial on telephonedelivered ACT versus telephone-delivered CBT in 121 uninsured callers to the South Carolina state quitline, Bricker 

and colleagues (2014a) found no significant difference in 

30-day point-prevalence quit rates at 6- month follow-up. 

In recent years, ACT has also been adapted and 

pilot tested as (a)  a smartphone application to reduce 

smoking (Singh et  al. 2017) and to motivate smoking 

cessation (Bricker et  al. 2014b; Bricker et  al. 2017) and 

(b) a web-based intervention (Bricker et al. 2013; Bricker 

et al. 2018). For example, in a single-arm pilot trial of a 

smartphone application of ACT (SmartQuit® 2.0) among 

smokers, Bricker and colleagues (2017) found that at 

2-month follow-up, quit rates were 21% for 7-day point 

prevalence (vs. 23% for SmartQuit®) and 11% for 30-day 

point prevalence (vs. 13% for SmartQuit®), and 75% of 

participants reduced their smoking frequency (vs. 57% for 

SmartQuit®). Among program completers (24%  of the 

total sample), quit rates were 33% for 7-day point prevalence and 28% for 30-day point prevalence, and 88% of 

participants reduced their smoking frequency. ACT has 

also been explored in specific populations, including 

smokers with depressive symptoms (Jones et  al. 2015), 

smokers with bipolar disorder (Heffner et al. 2015, 2018), 

veterans with posttraumatic stress disorder (Kelly et  al. 

2015), and female smokers with cessation-related weight 

concerns (Bloom et al. 2017). More research is needed to 

better understand populations and delivery modalities for 

which ACT is particularly promising as a smoking cessation approach compared with existing cognitive therapies.

Contingency Management and Monetary 

Incentives

A large body of evidence (Ainscough et al. 2017) supports contingency management, which involves the use of 

incentives (including money, gift cards, or other tangible 

goods) to motivate people to change health behaviors, 

including motivating them to maintain abstinence from 

substance use over an extended period of time (Lussier 

et al. 2006). Monetary incentives for quitting or not initiating smoking or tobacco use, such as paying persons for 

engaging in cessation services and for achieving cessationrelated outcomes (e.g.,  abstinence or participation in 

treatment), have been tested alone and in combination 

with cessation medication or counseling as an approach to 

increase compliance with nicotine dependence treatment 

and sustained abstinence from tobacco use. In a metaanalysis of the use of incentives for smoking cessation, 

Cahill and colleagues (2015) analyzed 21 trials of incentive 

programs that were implemented in a variety of settings 

for mixed populations and special groups (e.g., pregnant 

women). The OR for quitting with incentives (compared 

with controls) at the longest period of follow-up (at least 

6  months) was 1.42 (95%  CI, 1.19–1.69). Additionally, 

incentive-based programs increased rates of smoking cessation among pregnant women at both end-of-pregnancy 

and postpartum assessments. In an analysis by Cahill and 

Perera (2011), the primary benefit of incentive-based interventions was often seen only while the incentive was still in 

place. Only one of the reviewed studies (Volpp et al. 2009) 

in the analysis showed a statistically significant effect of the 

incentive program after the active incentive phase ended.

A key factor in the success of incentives in motivating smokers to quit may be the behavior that is being 

incentivized (quitting vs. engaging in treatment) and 

how the incentive is framed (reward vs. punishment). 

For example, in the study by Cahill and Perera (2011), 
A Report of the Surgeon General

500 Chapter 6

the participating employer opted to charge employees 

who smoked more for their insurance, rather than paying 

them for quitting, because nonsmoking employees viewed 

the latter approach as unacceptable. However, charging 

employees who smoke higher insurance premiums could 

have potential unintended consequences, such as leading 

them to forgo health insurance because it is too expensive 

or to conceal their smoking status to avoid the surcharges, 

making it harder to provide these employees with quitting support (Friedman et al. 2016; also see Chapter 7). As 

this example shows, contingency management could have 

unintended effects if improperly designed. 

In 2011, the Centers for Medicare & Medicaid 

Services (CMS) launched the Medicaid Incentives for 

Prevention of Chronic Disease program in 10 states to 

assess the effectiveness of incentives in increasing certain 

preventive health behaviors, such as weight management 

and smoking cessation, among Medicaid beneficiaries as 

a strategy to improve the management of noncommunicable disease (CMS 2011, 2018). The results described in 

the final report on the project generally support the incentive approach (Hoerger et al. 2017). Five states (California, 

Connecticut, New Hampshire, New York, and Wisconsin) 

implemented incentive programs for smoking cessation. In 

the three states that tested impacts on program utilization 

(Connecticut, New Hampshire, and Wisconsin), incentives 

significantly increased the use of program services. Four 

of the states (California, Connecticut, New Hampshire, 

and Wisconsin) assessed the impact of incentives on rates 

of smoking cessation (which were biochemically verified 

in Connecticut, New Hampshire, and Wisconsin and selfreported in California); in all four states, rates of smoking 

cessation increased among those in the incentive group 

relative to those in the control group (Witman et al. 2018). 

In general, motivation to quit and rates of cessation may increase while monetary incentives are in place, 

but these outcomes are rarely sustained after such incentives are removed. It is unclear whether a monetary incentive-based strategy is practical outside a research setting, given the reluctance of employers and insurers to 

pay smokers to quit and the potential unintended consequences of charging smokers more for health insurance. More research is needed to (a) explore whether any 

approaches to incentivizing smoking cessation sustain 

their effects over time and do not lead to counterproductive outcomes and (b) identify what types of approaches 

meet these criteria.

Relapse Prevention and Recovery

Most smokers make multiple quit attempts before 

finally succeeding in quitting for good. Indeed, one study 

estimated that smokers may make an average of 30  or 

more quit attempts (i.e., serious attempts to quit smoking) 

before eventually succeeding (Chaiton et  al. 2016). This 

means that most quit attempts end in relapse. Most 

relapses occur during the first few hours, days, or weeks 

of a quit attempt (Fiore et al. 2008). Although the risk of 

relapse declines over time, even former smokers who have 

quit for months or years can relapse (Hawkins et al. 2010).

Several treatment strategies include components designed to prevent relapse or to help smokers 

recover from relapses. Examples include relapse prevention therapy, which equips smokers with skills for 

avoiding or coping with high-risk environments and situations (Collins et al. 2010); acceptance and commitment 

therapy, which teaches smokers coping strategies to help 

them avoid lapsing into states of distress or giving in to 

strong urges to smoke (Bricker et al. 2014b); and motivation-enhancing interventions, which have been used to 

encourage smokers to make a quit attempt even if they are 

not ready to quit (Fiore et al. 2008; Lindson-Hawley et al. 

2015). Each of these treatment models has demonstrated 

efficacy that is greater than brief advice (Lindson-Hawley 

et al. 2015) but not substantially greater than an equalintensity intervention based on the Clinical Practice 

Guideline that addresses relevant risks of smoking, 

rewards of quitting, roadblocks to cessation, and repetition at each visit (Catley et al. 2016).

Despite the availability of relapse prevention and 

recovery interventions, scientific literature reviews on the 

topic highlight the difficulty of preventing and addressing 

relapse (Agboola et  al. 2010; Hajek et  al. 2013c). For 

example, in a Cochrane Review meta-analysis of relapse 

prevention interventions among smokers during the first 

6 months of a quit attempt, Hajek and colleagues (2013c) 

found no evidence of benefit for additional post-cessation 

behavioral interventions or combined behavioral and 

pharmacologic interventions, either overall or for any 

subgroup. Many of the studies included in the Cochrane 

Review used small sample sizes and had limited statistical 

power to detect modest but potentially clinically significant effects, and the interventions may have been insufficient to achieve the desired effect. In addition, some 

studies focused on long-term abstinence. Therefore, these 

studies may have overlooked potentially beneficial recycling or recovery effects that result in increased frequency 

of secondary quit attempts. In a more recent review, 

Livingstone-Banks and colleagues (2019) found that the 

evidence does not support the use of behavioral treatments to help prevent relapse following smoking cessation 

among assisted abstainers. Instead, the most promising 

treatments involved extending treatment with certain 

pharmacotherapy, namely varenicline; extending treatment with bupropion was not shown to prevent relapse. 
Interventions for Smoking Cessation and Treatments for Nicotine Dependence 501

Smoking Cessation

Furthermore, the review found insufficient evidence on 

extending treatment with NRT in preventing relapse in 

assisted abstainers. However, evidence for extending NRT 

in unassisted abstainers suggested a benefit. At present, 

more research is needed on specific behavioral interventions that can be delivered during the early stages of cessation to help smokers avoid short-term relapse. 

Intervention Delivery Modalities

Research demonstrates that behavioral therapy 

approaches for smoking cessation can be delivered effectively through face-to-face counseling (individually or in 

groups) and brief clinical interventions (Fiore et al. 2008); 

and technology-mediated approaches, including telephone-based tobacco quitlines, mHealth, short message 

service (SMS) texts, web-based interventions, and smartphone applications; and, under certain circumstances, tailored self-help materials (The Community Guide 2011b, 

2012b; Whittaker et al. 2012; Stead et al. 2013b, 2017; 

Lancaster and Stead 2017). 

Self-Help Materials

In general, self-help materials for smoking cessation that are not tailored to a particular person or group 

have limited effectiveness when they are not coupled with 

in-person or technology-based interventions (Fiore et al. 

2008). In a review of behavioral counseling interventions 

for tobacco cessation among adults, Patnode and colleagues (2015) did not find evidence of increased cessation 

in a comparison between nontailored self-help materials 

and no self-help materials. However, tailored self-help 

materials that are based on specific characteristics or concerns of smokers have been shown to be effective (Fiore 

et al. 2008; Patnode et al. 2013). Additionally, a Cochrane 

Review found some efficacy for tailored self-help materials in print, audio, and video forms compared with nontailored materials, but the absolute size of the effect was 

small (RR = 1.28; 95% CI, 1.18–1.37), and the review did 

not examine Internet-based materials (Hartmann-Boyce et 

al. 2014). Still, an effect size of 1.28 can be consequential 

given how inexpensive tailored self-help materials are relative to cessation medications or multisession counseling. 

The Cochrane Review also concluded that, although tailored self-help materials may offer some benefit, smokers 

trying to quit should also seek out more intensive cessation treatments.

Face-to-Face Counseling

Face-to-face counseling—whether delivered in 

traditional healthcare settings, behavioral healthcare 

settings, or community settings—has traditionally been 

the gold standard for behavioral treatment of nicotine 

dependence, and its effectiveness is well-established in the 

scientific literature (Fiore et al. 2008). Noting substantial 

variability in the specific content of counseling delivered 

and in the skills of those delivering the counseling, the 

Clinical Practice Guideline concluded that individual inperson counseling achieved an average abstinence rate for 

cigarette smoking of 16.8%, compared with 10.8% for the 

control conditions (OR = 1.7; 95% CI, 1.4–2.0) (Fiore et al. 

2008). In contrast, in-person group counseling achieved a 

13.9% abstinence rate (OR = 1.3; 95% CI, 1.1–1.6). 

In a Cochrane Review, Lancaster and Stead (2017) 

assessed the effectiveness of intensive counseling delivered 

by a cessation counselor on a one-on-one basis. All 49 RCTs 

they reviewed, which included approximately 19,000 participants combined, contained a face-to-face intervention 

component; however, some trials also included the use 

of other behavioral intervention modalities. The review 

concluded that individual counseling was more effective 

than minimal contact (brief advice, usual care, or self-help 

materials) when pharmacotherapy was not systematically 

offered to any participants (RR = 1.57; 95% CI, 1.40–1.77). 

Additionally, there was moderate evidence of a benefit for 

(a)  the addition of intensive counseling (vs.  usual care) 

when cessation pharmacotherapy was offered to all participants (RR = 1.24; 95% CI, 1.01–1.51) and (b) more intensive counseling compared with brief counseling (with 

or without the addition of cessation pharmacotherapy) 

(RR = 1.29; 95% CI, 1.09–1.53). 

Brief Clinician-Delivered Advice

Clinical and other healthcare settings are a natural channel for delivering brief cessation interventions 

because at least 70% of tobacco users visit a physician 

each year (Fiore et al. 2008), almost one-third visit a dentist (Fiore et  al. 2008; Carson et  al. 2012), and millions 

see a specialist or are hospitalized (National Center for 

Health Statistics 2018). Encounters with clinicians represent a key opportunity to engage smokers in cessation 

treatments because clinical visits can provide teachable 

moments for patients who are experiencing or at risk for 

tobacco-related diseases (Fiore et  al. 2008). Clinicians 

can take advantage of this opportunity and enhance the 

impact of their advice to quit by delivering this advice in 

a personalized manner that places it in the context of the 

patient’s specific diagnosis and health history (Fiore et al. 

2008). Furthermore, smokers respect and trust physicians and expect them to address their tobacco use (Quinn 

et  al. 2005) and are more satisfied with healthcare providers when the providers discuss cessation with them 

(Bernstein and Boudreaux 2010; Winpenny et  al. 2017; 

Holla et al. 2018). 
A Report of the Surgeon General

502 Chapter 6

Evidence increasingly suggests that healthcare 

providers other than physicians can also be effective in 

advising smokers to quit. For example, in a Cochrane 

Review of 11 studies, Rice and colleagues (2017) found 

moderate evidence that behavioral support provided 

by nurses can motivate and sustain smoking cessation. In another Cochrane Review of 14 studies totaling 

more than 10,500 participants, Carr and Ebbert (2012) 

found evidence suggesting that behavioral interventions conducted by oral health professionals (e.g., dentists and dental hygienists) as part of an oral examination in a dental office or other community setting could 

increase cessation rates in cigarette smokers and users 

of smokeless tobacco (pooled OR = 1.71; 95% CI, 1.44–

2.03). Research is also emerging about the role that pharmacists and community pharmacies can play in helping 

to promote tobacco cessation (Augustine et al. 2016; 

Greenhalgh et al. 2016).

Based on the strong evidence base for brief tobacco 

cessation interventions, USPSTF (2015) recommends, as 

a “Grade A” recommendation, that clinicians deliver such 

interventions to all adult smokers. Even brief (<3 minutes) advice from a physician improves cessation rates 

(OR = 1.66; 95% CI, 1.42–1.94) (Stead et al. 2013a) and is 

highly cost-effective (Maciosek et al. 2017a). 

As a framework, the 5 A’s method is considered the 

gold standard for delivering a brief tobacco cessation intervention. The 5 A’s method consists of the following steps: 

1. Ask all patients about tobacco use; 

2. Advise tobacco users to quit (e.g., “quitting is the 

best thing you can do for your health”);

3. Assess the patient’s willingness to make a quit 

attempt (e.g., “have you thought about quitting or 

are you interested in trying?”); 

4. Assist in the quit attempt with medications, counseling, and referrals to behavioral treatment programs; and 

5. Arrange follow-up (Table 6.1) (Fiore et al. 2008, p. 39). 

Implementation of the 5 A’s by physicians is effective in increasing tobacco cessation and quit attempts 

among patients and in increasing engagement among 

patients in other empirically validated cessation treatments (Quinn et al. 2009). Compared with patients who 

received only one or none of the 5 A’s, delivering all of the 

5 A’s increased patients’ receipt of counseling (OR = 11.2; 

95% CI, 7.1–17.5), use of FDA-approved cessation medications (OR = 6.2; 95% CI, 4.3–9.0), and combined use of 

counseling and medication (OR = 14.6; 95% CI, 9.3–23.0) 

(Kruger et al. 2016).

In practice, however, despite the robust evidence for 

the effectiveness of brief tobacco interventions, many clinicians do not consistently address tobacco use and nicotine dependence. For example, in nationally representative data from 2000 to 2015, Babb and colleagues (2017) 

found that 57% of smokers who had seen a health professional in the past year reported receiving advice to quit. 

In an earlier study, King and colleagues (2013) found 

that patient reports of their physicians providing each of 

the 5 A’s typically decreased as the steps progressed, with 

“Asking” about tobacco use (87.9%) being more prevalent 

than “Assisting” with a quit attempt (78.2% of those who 

wanted to quit) and the prevalence of “Assisting” being 

far more prevalent than “Arranging for follow-up” (17.5% 

overall). Thus, in practice, clinicians are rarely performing 

all five actions in the 5 A’s approach. One way to address 

this problem is by delegating some of the steps of the 5 A’s 

(e.g., Ask, Assist, Arrange) in whole or in part to other 

members of the healthcare team (e.g., nurses, physician 

assistants, roomers, etc.) (Fiore et al. 2008). This approach 

Table 6.1 The 5 A’s model for treating tobacco use and dependence

Ask about tobacco use • Identify and document tobacco use status for every patient at every visit.

Advise to quit • In a clear, strong, and personalized manner, urge every tobacco user to quit.

Assess readiness to make a quit attempt • Is the tobacco user willing to make a quit attempt at this time?

Assist in quit attempts • For the patient willing to make a quit attempt, offer medication and provide or refer 

for counseling or additional treatment to help the patient quit.

• For patients unwilling to quit at the time, provide interventions designed to increase 

future quit attempts.

Arrange follow-up • For the patient willing to make a quit attempt, arrange for follow-up contacts, 

beginning within the first week after the quit date.

• For patients unwilling to make a quit attempt at the time, address tobacco 

dependence and willingness to quit at next clinic visit.

Source: Fiore and colleagues (2008, p. 39).
Interventions for Smoking Cessation and Treatments for Nicotine Dependence 503

Smoking Cessation

lessens the burden on physicians and emphasizes the 

importance of quitting to patients (Fiore et al. 2008).

A diagnosis of a tobacco-related disease has been 

associated with an increase in quit attempts, use of cessation resources (Patel et al. 2009; Schauer et al. 2014b; 

Gallaway et al. 2019), and cessation and can provide a teachable moment for patients, especially because quitting can 

often improve a patient’s prognosis or symptoms. Studies 

indicate that healthcare providers may be leveraging this 

opportunity. For example, in a study of patient-reported 

receipt of the 5 A’s in a nationally representative population 

of past-year cigarette smokers with and without chronic 

obstructive pulmonary disease (COPD), Schauer and colleagues (2016c) found that patients with COPD were more 

likely than those without COPD to receive each step in the 

5  A’s approach: Ask  =  95.4% vs. 85.8%; Advise  =  87.5% 

vs. 59.4%; Assess = 63.8% vs. 37.9%; Assist = 58.6% vs. 

34.0%; and Arrange = 14.9% vs. 5.2%. 

Barriers that can prevent clinicians from consistently conducting brief cessation interventions include 

time constraints; a lack of knowledge, training, and confidence; inadequate clinical and/or institutional support; 

a lack of adequate reimbursement for delivering tobacco 

treatment; and inadequate or confusing insurance cessation coverage (Fiore et al. 2008; Sheffer et al. 2012). 

Concerns about the lack of adequate training to effectively 

deliver cessation interventions are also reported by other 

healthcare providers, such as nurses, psychologists, and 

social workers (Steinberg et al. 2006a,b; Applegate et al. 

2008; Sheffer et al. 2012).

Alternative Approaches to the 5 A’s

Research supports the value of alternative treatment approaches that do not deliver all steps of the 5 A’s 

approach in the clinical setting. One such alternative that 

is widely used is the Ask-Advise-Refer (AAR) approach, 

which involves a provider in a clinical setting Asking 

about tobacco use; Advising patients to quit; and Referring 

interested patients to another cessation resource, such 

as a quitline (see Chapter 7), to complete the remaining 

“Assess,” “Assist,” and “Arrange” steps (Schroeder 2005; 

Gordon et al. 2010). Gordon and colleagues (2010) compared the use of the 5 A’s with the use of the AAR approach 

in 68 dental clinics. At 12 months, participants receiving 

either the 5 A’s or the AAR were more likely to report 

tobacco cessation than those who received only usual care. 

Additionally, there was no significant difference (using a 

threshold of p <0.05) in rates of 9-month prolonged cessation between participants receiving the 5 A’s method and 

the AAR approach (3% vs. 2%, p <.10 for 9 months of prolonged abstinence) (Gordon et al. 2010).

Limited research supports a third approach, AskAdvise-Connect (AAC). Compared with AAR, AAC provides 

a more active and direct connection to an outside cessation 

resource (Vidrine et al. 2013a,b). One example of providing 

such a direct connection is referring smokers to tobacco 

quitlines via an electronic referral or “eReferral” that 

securely transfers patient registration information from 

electronic health records to the quitlines (Boyle et al. 2011, 

2014; Sheffer et al. 2012; Adsit et al. 2014; Tindle et al. 2016) 

(see Chapter 7 for more details on electronic health records 

and eReferrals). Some research suggests that AAC may be 

more effective than AAR in reaching smokers and engaging 

them in treatment. Specifically, in a pair-matched, twotreatment-arm, group-randomized study conducted in 

10 family practice clinics in one metropolitan area, 7.8% 

of all identified smokers enrolled in treatment in the AAC 

arm compared with just 0.6% who enrolled in the AAR arm 

(OR = 11.6; 95% CI, 5.5–24.3) (Vidrine et al. 2013a).

Finally, because many smokers are ambivalent 

about quitting or have transient motivation to quit, a 

fourth hypothetical version of the 5 A’s might build on 

such approaches as the 5 R’s (Relevance, Risks, Rewards, 

Roadblocks, and Repetition) (Agency for Healthcare 

Research and Quality 2012), which is used for smokers 

who are not yet ready to quit and focuses on providing 

interventions and supports to all smokers, even those who 

are initially assessed as not ready to quit. This approach is 

appealing from a theoretical standpoint because of the lack 

of clear evidence demonstrating that a very brief assessment of readiness to quit is sufficient to withhold an offer 

of more robust cessation support to these individuals. One 

potential downside of this approach could be that providing support to smokers who are not ready to quit could 

turn out to be time-consuming and inefficient. To date, 

randomized trials have not assessed this approach. 

As tobacco cessation interventions are increasingly 

integrated into inpatient care and into care in other settings, such as pharmacies and behavioral health treatment facilities, updates to the 5 A’s model may emerge 

that more explicitly coordinate and distribute cessation 

interventions across an integrated care team and across 

different clinical environments.

Intensive Face-To-Face Counseling

Intensive in-person behavioral treatment, which is 

sometimes combined with pharmacologic interventions, 

typically consists of multiple face-to-face counseling sessions that last long periods of time (e.g., ≥10 minutes) by 

clinicians who have been trained in specialized smoking 

cessation interventions (Fiore et  al. 2008). Although 

intensive interventions are intended primarily for moderately to heavily addicted smokers, the effectiveness and 

cost-effectiveness of such interventions are not limited 

to heavy or highly dependent smokers (Fiore et al. 2008; 

USPSTF 2015). A range of intensive treatment programs 
A Report of the Surgeon General

504 Chapter 6

are available at the individual and group levels in some 

communities, worksites, and healthcare systems (Institute 

of Medicine 2007). However, availability varies widely 

from community to community, and geographic location and temporal availability are major barriers to utilization. In practice, such intensive cessation approaches 

are generally the exception rather than the rule in the 

United States. Compared with the United States, some 

countries have invested more heavily to ensure that most 

smokers have access to intensive face-to-face counseling. 

For example, in addition to making brief cessation interventions delivered by primary care physicians and some 

pharmacists widely available, the United Kingdom has 

established Stop Smoking Services, which mainly target 

highly addicted smokers and are staffed by counselors 

who are trained in behavioral approaches to smoking cessation (Dobbie et al. 2015; Public Health England 2017). 

Both intensive individual and group cessation treatments 

have been shown to be effective when delivered outside of 

healthcare clinics, particularly in workplace settings. For 

example, Cahill and Lancaster (2014) reported on rates of 

tobacco cessation in eight trials in workplace settings that 

involved intensive group treatments (N = 1,309) and individual treatments (N = 3,516). Relative to controls, the OR 

for successful quitting among those in the intensive group 

treatments (OR = 1.71; 95% CI, 1.05–2.80) was generally 

comparable in magnitude to that for those receiving individual treatments (OR  =  1.96; 95%  CI, 1.51–2.54), suggesting that well-designed group counseling can be effective in workplace settings.

Although a strong evidence base exists for in-person 

behavioral approaches to treating tobacco use and nicotine 

dependence, few U.S. smokers use face-to-face individual 

and group counseling when trying to quit, possibly because 

of a lack of investment in these approaches and practical 

barriers to use (e.g., time, transportation, schedule, etc.) 

(Dobbie et al. 2015; Public Health England 2017). For 

example, in a U.S. study, Babb and colleagues (2017) found 

that in 2015 31.2% of U.S. adult cigarette smokers reported 

using cessation counseling and/or medication when trying 

to quit, 6.8% reported using counseling, 29.0% reported 

using medication, and 4.7% reported using both counseling 

and medication. In terms of specific types of counseling, 

4.1% of smokers reported using a telephone quitline; 2.8% 

one-on-one counseling; and 2.4% a stop-smoking clinic, 

class, or support group (Babb et al. 2017). 

Technology-Mediated Delivery Approaches

Evidence supports the effectiveness of certain nonface-to-face delivery approaches for tobacco cessation, 

including telephone-based quitlines (The Community Guide 

2012a) and mHealth-based interventions (The Community 

Guide 2011b). These approaches have characteristics that 

can remove or reduce time, transportation, and child care 

issues that may hinder face-to-face service delivery, thereby 

potentially leading to more widespread use. The following 

section reviews technology-mediated tobacco cessation 

intervention delivery approaches, including quitlines, SMS 

texting, web-based interventions, and smartphone applications. Telehealth approaches, which are discussed later 

in the “Emerging Behavioral Treatments” section of this 

chapter, are another emerging technology that can be used 

to deliver tobacco cessation interventions. 

Tobacco Quitlines

Staffed by trained counselors or coaches, tobacco 

quitlines typically deliver a variety of services, including 

individual counseling, practical information on how to quit, 

referrals to other cessation or health-related resources, 

mailed self-help materials, information on FDA-approved 

cessation medications, and, in some cases, provision of limited quantities of free or discounted cessation medications 

(Keller et al. 2010; Anderson 2016). Publicly funded quitlines are available at no cost to U.S. residents in every state, 

the District of Columbia, Guam, and Puerto Rico (North 

American Quitline Consortium n.d.b). However, specific 

services vary across states, largely as a result of funding constraints that vary across states and jurisdictions and over 

time (Centers for Disease Control and Prevention [CDC] 

2014; Anderson 2016). In addition to publicly funded state 

quitlines, some public and private health insurance plans 

and employers also offer quitline services (CDC 2014). 

Since the 1990s, a large body of clinical literature 

has consistently demonstrated the effectiveness of tobacco 

quitlines (Zhu et  al. 1996; Fiore et  al. 2008). Although 

research on single- and multi-call quitline protocols has 

demonstrated that both are effective, better outcomes have 

been reported for multi-call approaches. Better outcomes 

have also been documented for proactive quitline services, which make multiple outbound calls to engage the 

tobacco user in ongoing treatment, compared with reactive quitline services, which simply respond to incoming 

calls from tobacco users. For example, in a meta-analysis of 

49 studies that compared proactive quitlines with reactive 

quitlines, The Community Guide (2012b) estimated that 

proactive quitlines yielded a median 3.1-percentage-point 

increase (0.5–3.3  percentage points, 12  studies) in quitting and a 4.2 percentage-point increase when promoted 

through mass-reach health communication interventions. 

Similarly, in a Cochrane Review of 77  trials that 

assessed counseling provided through quitlines, Stead and 

colleagues (2013b) concluded that multiple sessions of 

proactive telephone counseling significantly boosted rates 

of smoking cessation (nine studies; >24,000 participants; 

RR for cessation at longest follow-up  =  1.37; 95%  CI, 

1.26–1.50). There was some evidence of a dose-response 
Interventions for Smoking Cessation and Treatments for Nicotine Dependence 505

Smoking Cessation

effect—that is, more completed quitline counseling calls 

yielded higher rates of cessation. Even reactive calls to 

quitlines were effective in increasing cessation (51 studies, 

>30,000  participants, RR for cessation  =  1.27; 95%  CI, 

1.20–1.36). 

A toll-free national portal (1-800-QUIT-NOW) operated by the National Cancer Institute (NCI) links callers to 

their state quitline based on their area code. An electronic 

telecommunications device for the deaf (TDD) is also 

available to serve persons who are deaf or hard of hearing. 

From 2010 to 2015, state quitlines received an estimated 

1.1–1.3 million calls annually and provided cessation 

counseling and/or cessation medications to an estimated 

342,000–475,000 tobacco users each year (CDC, National 

Quitline Warehouse Database, unpublished data).

NCI also operates 1-855-DÉJELO-YA (1-855-335-

3569), a national portal that routes Spanish-speaking 

callers to Spanish-language services available through their 

state quitlines. From February 2013 (the portal’s inception) 

through December 2018, 1-855-DÉJELO-YA received more 

than 40,000 calls (CDC, NCI, unpublished data).

In addition, the Moores Cancer Center at the 

University of California–San Diego operates a nationwide Asian Smokers’ Quitline, which offers direct counseling services in Chinese, Korean, and Vietnamese (Asian 

Smokers’ Quitline n.d.). Nearly 5,800 callers from 48 states 

enrolled in the Asian Quitline between 2012 and 2014; 

31% spoke Chinese (Cantonese or Mandarin), 38% spoke 

Korean, and 31% spoke Vietnamese (Kuiper et al. 2015). 

Nearly all eligible callers to the Asian Quitline (99%) 

received nicotine patches. Approximately 85% of smokers 

who called the Asian Quitline enrolled in counseling, completing an average of four sessions (Kuiper et al. 2015). 

Quitline counseling is readily accessible because 

it is free, convenient, and confidential, and it removes 

or reduces barriers related to time, transportation, child 

care, and other factors (World Health Organization [WHO] 

2011). As a result, quitline counseling has the potential for 

broad reach. Quitline counseling has also been found to 

be effective with an array of subpopulations (BaezcondeGarbanati et  al. 2011). Tobacco users can be connected 

with a quitline in several ways: by calling directly; by 

having a healthcare provider’s office fax, send an online 

referral, or submit an eReferral through the patient’s electronic health record; by sending an e-mail; or by enrolling 

online. Most state quitlines provide at least one counseling 

session to any adult tobacco user who calls, and many state 

quitlines provide a multi-call program that includes both 

reactive and proactive calls. Some state quitlines prioritize 

multi-call services for subpopulations with a higher prevalence of tobacco use and/or limited access to other tobacco 

cessation services (e.g., persons who lack health insurance 

or are unemployed) (Anderson 2016). A study of quitline 

eReferrals in Wisconsin randomized 23  primary care 

clinics from two healthcare systems to one of two methods 

for referring adult patients who smoked to the Wisconsin 

quitline: a paper-based, fax-to-quit referral process or an 

eReferral process (Fiore et al. 2019). The eReferral process 

involved sending referrals to the quitline from patients’ 

electronic health records and receiving outcome reports 

from the quitline back into the electronic health records. 

The fax referral process transmitted the same information in both directions via fax. A total of 14,636 smokers 

were seen in the two systems. Compared with clinics that 

were randomized to the fax referral process, clinics that 

were randomized to the eReferral process generated quitline referral rates that were 3- to 4-times higher and also 

generated higher rates of connecting patients with quitlines (i.e., having patients accept a quitline call and at least 

begin the process of registering for quitline services). The 

eReferral method generated especially high rates of referrals among Medicaid recipients. The study, which was 

the first randomized study of this topic, concluded that 

eReferrals provide an effective means of referring patients 

who smoke to quitline services.

A major innovation in quitline services that occurred 

over the past decade was the integration of NRT and, in 

some cases, other FDA-approved cessation medications 

into state quitline services, along with counseling. A series 

of randomized and quasi-randomized trials (Cummings 

et al. 2006; Hollis et al. 2007; Tinkelman et al. 2007) demonstrated that quitlines can feasibly and safely provide NRT 

to callers, either directly via mail order or by pharmacy 

voucher. This involved having quitlines screen callers for 

the medical appropriateness of NRT use, educate callers 

on how to properly use the NRT, and continue to provide 

callers with behavioral counseling. Making cessation medication available to callers and promoting its availability 

results in more smokers calling quitlines and has the potential to increase quit rates among callers by providing them 

with the optimal combination of cessation counseling plus 

medications (An et  al. 2006). Even 2-week NRT “starter 

kits” have demonstrable benefits, including increased call 

volume to quitlines, higher quit rates, and increased caller 

satisfaction with the quitline (Bush et al. 2008; Deprey et al. 

2009; Kerr et  al. 2018). Distributing NRT through quitlines can be cost-effective (Fellows et al. 2007; Cummings 

et  al. 2011). For example, Fellows and colleagues (2007) 

estimated that the total cost per quit was $2,688 lower for 

callers who received free NRT ($1,050) compared with persons who called the Oregon quitline before it began offering 

the nicotine patch to callers ($3,738).

The reach of state quitlines varies across states, over 

time, and by demographic factors, such as race/ethnicity 

(North American Quitline Consortium n.d.a). Despite 

reaching thousands of smokers each year in most states, 
A Report of the Surgeon General

506 Chapter 6

state quitlines reach an average of 1% of smokers annually 

(CDC 2014). Data suggest that even among smokers who 

tried to quit in the previous year and were aware of quitlines, quitline reach was around 8% (Schauer et al. 2014a). 

This limited awareness and reach, along with the variation 

in quitline services and eligibility for these services across 

states and over time, are largely the result of limited state 

funding for operating and promoting quitlines (e.g., state 

quitline expenditures) (CDC 2004; Schauer et al. 2014a). 

States have developed the capacity to carefully titrate their 

activities to promote quitlines and the level of quitline services they provide to match available funding. Some states 

have been able to temporarily attain higher levels of reach, 

in some cases higher than 6%, during periods when they 

can fund quitlines at higher levels, often while also conducting specific policy and promotional efforts that drive 

increased calls to the quitline (Woods and Haskins 2007; 

Mann et al. 2018).

Call volume to quitlines is highly sensitive to promotional activities (Anderson 2016). For example, Tips 

From Former Smokers (Tips), a national tobacco education campaign conducted annually by CDC for varying 

periods of time from 2012 to 2019, includes a message 

on the majority of its television ads directing smokers to 

call 1-800-QUIT-NOW for free help quitting. From 2012 

to 2018, this campaign generated more than 1.3 million 

additional calls to 1-800-QUIT-NOW (Nathan Mann, RTI 

International, personal communication, May 6, 2019). 

Call volume to 1-800-QUIT-NOW consistently increases 

when the campaign airs and decreases when it goes off the 

air (Zhang et al. 2016; McAfee et al. 2017; Murphy-Hoefer 

et al. 2018). 

In part, to maintain or improve their reach, state 

quitlines increasingly offer ancillary cessation services, 

such as Internet interventions, e-mail, chat, texting, and 

the dispensing of NRT both alone and in combination with 

counseling (Anderson 2016; Keller et al. 2016). This shift 

in quitline practice stems in part from the recognition that 

many younger adults prefer to access cessation assistance 

through these alternative channels rather than over the 

telephone (Dreher et al. 2015). For example, to increase 

both reach and quitting behavior, Minnesota implemented 

a model for state quitline services in 2014 that expanded 

tobacco users’ options for accessing cessation services, 

allowing tobacco users to enroll via telephone or online 

and to choose one or more cessation services from a menu 

of options that includes quitline counseling, a medication starter kit, text messaging, an e-mail program, and 

a quit guide (Keller et  al. 2016). Between March 2014 

and February 2015, 15,861  unique tobacco users registered for cessation services in the state—a 169% increase 

over calendar year 2013. More than four in five (83.7%) 

of the participants made a quit attempt, and the 30-day 

point-prevalence abstinence rate (among responders) 

was 26.1% for the overall program (regardless of services 

used); 29.6% for quitline services; and 25.5% for individual non-quitline services. Thus, the reach of quitlines 

can be expanded, and new populations can be engaged in 

cessation services when quitlines (a) broaden their cessation service offerings beyond traditional telephone-based 

quitline services and (b) allow tobacco users to choose the 

service that best meets their needs and suits their preferences (Keller et al. 2016). 

Mobile Health Intervention Strategies

Desktop or laptop computer-based interactive program modalities for delivering smoking cessation support 

have been developed and tested (USPSTF 2015), first via 

programs operated from a CD-ROM or hard drive, later via 

Internet downloads, and more recently from “the cloud” 

(Strecher et al. 2005; Haskins et al. 2017). The current 

state of science and technology also allows the leveraging 

of mobile phone and tablet applications (e.g., mHealth 

interventions) to deliver treatment for nicotine dependence (Whittaker et al. 2016). mHealth strategies can 

be broadly defined as the use of technology to remotely 

monitor, track, respond to, and/or deliver an intervention 

for health-related events. mHealth treatment platforms 

have expanded greatly during the past 20 years and especially in the past decade, with the development of electronic and mHealth technologies. These platforms include 

applications offered by for-profit and not-for-profit organizations and academic institutions and by federal agencies involving standardized text messages that enhance 

motivation to quit smoking or inform persons about quitting strategies, some of which offer real-time, live peer or 

professional advising or counseling (Smokefree.gov n.d.). 

Preliminary evaluations suggest that these applications 

benefit users (Cole-Lewis et al. 2016; Squiers et al. 2016, 

2017; Taber et al. 2016) and that the cost of delivery is low.

Uptake of mobile technologies has been seen across 

almost all segments of the U.S. population (Pew Research 

Center 2017b). In 2016, cell phone ownership and usage 

were widespread: 95% of American adults owned a cell 

phone; 77% had a smartphone; and ownership levels were 

generally similar across all categories of race/ethnicity, age, 

education level, income level, and rural versus urban status 

(Pew Research Center 2017b). Texting is common among 

cell phone users, and many smartphone users report using 

their phones for texting, accessing the Internet, watching 

videos, and using apps (applications). Importantly, despite 

the widespread adoption of mobile technology, some populations—including some low-income and rural individuals 

and veterans—do not have equal access to mobile technology (Koutroumpisa and Leiponenb 2016; Markham 

et al. 2016). 
Interventions for Smoking Cessation and Treatments for Nicotine Dependence 507

Smoking Cessation

Despite some remaining gaps in the availability and 

coverage of mobile technology, these technologies offer 

considerable potential to serve as platforms for delivering 

smoking cessation interventions. In 2011, the Community 

Preventive Services Task Force recommended mobile 

phone-based interventions, specifically automated texting programs, for tobacco cessation on the basis of sufficient evidence of their effectiveness in increasing tobacco 

use cessation among persons interested in quitting (The 

Community Guide 2011b).

Potential advantages of mHealth interventions 

include greater reach to some disproportionately impacted 

populations (Markham et al. 2016; Anguiano et al. 2017) 

and reduced costs because mHealth interventions can be 

less costly to provide than other behavioral interventions. 

In terms of reach, the Smokefree.gov initiative—a large 

federal mHealth behavioral intervention program that 

focuses primarily on smokers—reaches 5–6.5 million persons each year, including more than 3.6 million visitors 

to the Smokefree.gov website in 2018 (Yvonne Prutzman, 

NCI, personal communication, January  23, 2019). In 

addition, mHealth interventions may improve engagement through increased access to intervention services, 

decreased barriers to participation (e.g., by removing barriers related to scheduling, transportation, or child care), 

seamless integration of users’ interactions with treatment 

into their daily lives, and the ability to personalize treatment based on passively (e.g.,  GPS [global positioning 

system] location) or actively (e.g., self-report of craving) 

gathered information (Atienza and Patrick 2011; Nilsen 

et al. 2012; Free et al. 2013; Borrelli et al. 2015; Marzano 

et al. 2015). 

The potential benefits from mHealth interventions 

are tempered by several challenges, including (1) inconsistent access to cell phones among low-income populations (despite the increasing adoption of cell phones, 

low-income populations may still struggle to maintain 

cell phone contracts, have regular access to minutes, and 

have data plans that allow for repeated use of interventions), (2)  different types of devices (e.g.,  cell phone vs. 

smartphone), (3) possible sharing of devices among multiple users, (4) differences in fee structures and costs for 

using cell phones, (5) the challenges of delivering content 

to populations with low literacy, and (6)  lack of broadband coverage (Atienza and Patrick 2011; Katz et al. 2012; 

Free et al. 2013; Marzano et al. 2015; McClure et al. 2016; 

Federal Communications Commission n.d.). 

At this time, optimal methods are not in place to 

fully assess the expanding array of available mHealth cessation interventions. Future research should address 

the components of the Reach, Effectiveness, Adoption, 

Implementation, and Maintenance (RE-AIM) impact 

model (addressed later in this chapter) to determine the 

effectiveness of mobile cessation interventions under 

ideal conditions and their impact when used in real-world 

settings (Stearns et al. 2014). Research should include both 

process measures, such as engagement and reengagement, 

and measures of the interventions’ impact on quit attempts 

and successful quitting. In addition, assessing the comparative effectiveness and cost-effectiveness of mHealth 

cessation interventions relative to other modalities, such 

as in-person and quitline interventions, will be important. Because of the rapid cycle of technological development, the use of adaptive and iterative research methods 

in assessing development and performing evaluations may 

be necessary. Although opportunities are available for conducting large cohort studies at a relatively low cost, the 

potential for selection bias and other types of bias in such 

studies underscores a need for RCTs in clinical settings.

Short Message Service Texting Interventions. 

Interventions based on SMS texting—which involve 

sending automated, one-way messages—offer a low-cost, 

convenient method of delivering smoking cessation interventions. Text messaging is a basic feature of almost all cell 

phones, making the delivery of cessation interventions via 

SMS texts an accessible and promising mHealth platform. 

A series of three studies from New Zealand and the United 

Kingdom provided the initial evidence supporting the use 

of this platform for delivering smoking cessation interventions (Rodgers et al. 2005; Free et al. 2009, 2011). Notably, 

a large-scale RCT in the United Kingdom that compared 

smokers receiving a text-based intervention with controls 

who received SMS texts related to the importance of trial 

participation, found a significant difference in biochemically verified abstinence at 6-month follow-up: 9.2% of 

smokers in the texting intervention achieved abstinence 

versus 4.3% of smokers in the control group (RR = 2.14; 

95% CI, 1.74–2.63) (Free et al. 2011). A subsequent metaanalysis of a limited number of text-based cessation interventions found that, compared with control conditions, 

such interventions improved the 7-day point-prevalence 

of abstinence (OR = 1.38; 95% CI, 1.22–1.55) and continuous abstinence (OR = 1.63; 95% CI, 1.19–2.24) (ScottSheldon et al. 2016). 

Although the findings from studies of cessation texting interventions are generally encouraging, a review of 

these interventions found that, while smoking cessation 

outcomes measured at less than 6  months were better 

than those for controls, outcomes measured at 6 months 

or longer often failed to show differences between treatment and control groups (Scott-Sheldon et al. 2016). In 

addition, the review found that the studies’ findings were 

mixed and the analyses were based on a small number of 

RCTs. One reason for these mixed findings may be the 

substantial variation in key features of the interventions, 

including frequency of messages per day and per week; 
A Report of the Surgeon General

508 Chapter 6

length of programs; use of unidirectional versus bidirectional messages; and, to a lesser extent, message content. 

Another reason may be variation in study design, such as 

the endpoint used for measuring abstinence (Free et  al. 

2013; Kong et  al. 2014; Scott-Sheldon et  al. 2016). This 

variability has presented a challenge when interpreting 

findings from specific studies. Nevertheless, the overall evidence supports the efficacy of text-based smoking cessation 

treatment programs. However, to inform the optimization 

of treatment, more research is needed to better understand 

the contributions of various treatment elements. 

Web-Based Interventions. Web-based cessation 

interventions (i.e., cessation interventions delivered via the 

Internet) have the potential to achieve broad reach, as 88% 

of American adults report regularly accessing the Internet, 

including a majority of low-income Americans and members of various racial/ethnic groups (Pew Research Center 

2017a). However, evidence on the effectiveness of webbased smoking cessation interventions is mixed. Such 

interventions date back to the early 2000s, with studies 

exploring several approaches for delivering treatment 

and examining user behavior (Etter 2005; Stoddard et al. 

2005; Strecher et al. 2005; Cobb and Graham 2006). Initial 

research findings were inconsistent, and several reports 

found that websites frequently failed to deliver recommended elements of behavioral treatment for smoking 

cessation (Bock et al. 2004, 2008; Fiore et al. 2008). 

In its 2011 review, the Community Preventive 

Services Task Force found insufficient evidence to determine the effectiveness of Internet-based interventions 

in increasing tobacco cessation (The Community Guide 

2011a). Later, a study on web-based tobacco cessation 

interventions by Civljak and colleagues (2013) concluded 

that some Internet-based interventions, particularly interventions that are interactive and tailored to individuals, 

can assist in achieving longer term smoking cessation. 

However, trials that compared Internet interventions with 

usual care or self-help did not show consistent effects. As 

web-based interventions have grown more sophisticated, 

incorporating better website design and improved functionality, the efficacy of such interventions for smoking 

cessation has improved significantly (Graham et al. 2016). 

A meta-analysis of web-based cessation interventions 

found that, although sites with largely static content did 

not perform significantly better than printed materials 

in increasing abstinence (RR = 0.83; 95% CI, 0.63–1.10), 

sites that incorporated interactive elements significantly 

increased abstinence (RR = 2.10; 95% CI, 1.25–3.52) 

(Graham et al. 2016). Comparisons of web-based cessation interventions with face-to-face counseling and quitline counseling suggest that these different modalities 

have the potential to produce similar cessation outcomes 

(Graham et al. 2016; McCrabb et al. 2019).

In a meta-analysis, McCrabb and colleagues (2019) 

assessed the effectiveness of 45  RCTs of adult-focused 

Internet cessation programs, as well as the number and 

type of behavior change techniques employed in the intervention (Michie et al. 2013), to determine how behavior 

change techniques impact program effectiveness. The 

study found short-term effectiveness for all measured cessation outcomes (e.g.,  prolonged abstinence and 30-day 

point-prevalence abstinence) (OR = 1.29; 95% CI, 1.12–

1.50) and for long-term outcomes (OR  =  1.19; 95%  CI, 

1.06–1.35). Interventions used more behavior change 

techniques than comparison groups (6.6 vs. 3.1, p <.0002). 

Interventions that included goals and planning, social 

support, natural consequences, comparison of outcomes, 

reward and threat, or regulation were significantly associated with increased intervention effectiveness in the short 

and long terms, when compared with study arms that did 

not include the domain(s).

The fact that web technologies and web-based cessation interventions continue to evolve, along with the 

potential reach and customizability of web-based technologies, suggests that future interventions could further improve on current ones. For example, advances in 

web technologies could improve user experience, enhance 

content management, better incorporate interactive elements, and better integrate various types of media (e.g., 

videos and audio). The increasing penetration of smartphones and the broad availability of free Wi-Fi may also 

allow for access to the web in many nontraditional settings. In response to this changing landscape, many websites are using adaptive design (i.e., changing the format 

to match the type of device used) and are optimized for 

use on mobile devices (i.e., are designed to offer easy navigation and high-quality user experience when accessed 

via such devices). Such sites have the potential to achieve 

broad population-level reach and widespread engagement 

with target audiences. Taken as a whole, the available evidence suggests that web interventions with interactive 

components can increase abstinence to tobacco. As with 

text-based cessation programs, more research is needed to 

better understand the specific components that can further enhance the effectiveness of web-based interventions 

for smoking cessation.

Smartphone Applications. Although most mobile 

phone interventions have traditionally relied on text messaging platforms (Whittaker et  al. 2016), the increasing 

use of smartphones offers a platform to combine elements 

of texting and the web to create more interactive and 

visual interventions (Abroms et  al. 2011). In their 2013 

review of smartphone apps for smoking cessation, Abroms 

and colleagues (2013) identified 252 such apps for Apple’s 

iOS and 148 apps for Google’s Android operating systems. 

The review then analyzed nearly 100 of the most popular 
Interventions for Smoking Cessation and Treatments for Nicotine Dependence 509

Smoking Cessation

cessation apps and their adherence to an index criteria 

based on the Clinical Practice Guideline (Fiore et al. 2008). 

The average score suggested that overall levels of the apps’ 

adherence to evidence-based cessation approaches were 

low (Abroms et al. 2011). However, smartphone apps for 

smoking cessation continue to evolve, both as standalone 

interventions and in combination with other approaches 

to cessation interventions. For example, in 2017 FDA 

granted marketing authorization for a carbon monoxide 

breath sensor system that can be paired with a smartphone via Bluetooth technology to measure carbon monoxide in exhaled breath and show smokers in real time how 

their cigarette smoking is impacting their levels of carbon 

monoxide (FDAnews 2017). The Smokefree.gov initiative 

now includes two free smoking cessation apps: QuitGuide, 

which helps smokers understand their smoking patterns and build skills to quit, and quitSTART, which gives 

smokers tailored tips and motivation to quit. These federally funded apps provide opportunities to learn more about 

the components that make a smoking cessation smartphone application effective. In particular, more research 

is needed to assess the efficacy of smartphone applications 

that combine texting and web-based features.

As reviewed, a variety of technology-mediated 

approaches exist to deliver behavioral interventions for 

smoking cessation, and these interventions stand to 

further increase the reach of cessation interventions. 

However, technologies are evolving, as are the ways in 

which people interact with and use technology. Therefore, 

ongoing research is warranted to ensure that technologybased approaches to cessation remain relevant and meet 

current user preferences. The elements that make a particular technology effective for cessation may shift as technologies evolve. For example, preferences for texting may 

shift as that technology becomes integrated into smartphone applications and user interfaces.

In summary, a variety of behavioral and counseling 

approaches are available through various delivery modalities to motivate and aid successful smoking cessation. 

However, most smokers still try to quit on their own without 

using behavioral or counseling interventions. Therefore, 

innovative, technology-based delivery modalities have the 

potential to help increase the reach and use of these interventions, but more research is needed to better understand 

the impact that different delivery modalities have on motivating and sustaining cessation in different subpopulations.

Pharmacologic Treatments

Nicotine is the drug in tobacco that leads to addiction (USDHHS 1988). Epidemiologic and laboratory 

evidence indicates that nicotine delivered in tobacco 

products is substantially more addictive than nicotine 

delivered through current medications (USDHHS 2010). 

In addition to behavioral and environmental components, 

constituents other than nicotine in tobacco products and 

product delivery methods play critical supporting roles in 

promoting nicotine addiction. A major conclusion from 

the 2010 Surgeon General’s report is, “Sustained use and 

long-term exposures to tobacco smoke are due to the powerfully addicting effects of tobacco products, which are 

mediated by diverse actions of nicotine and perhaps other 

compounds, at multiple types of nicotinic receptors in the 

brain” (USDHHS 2010, p.  9). The general rationale for 

having smokers use smoking cessation medications as part 

of a quit attempt is to reduce physical symptoms resulting 

from nicotine withdrawal, thus allowing smokers to focus 

on the behavioral and psychological aspects of quitting 

smoking (Prochaska and Benowitz 2016). Cessation medications also have the additional benefit of eliminating 

or greatly reducing the immediate reinforcing effects of 

nicotine absorbed from tobacco smoke by desensitizing 

the nicotinic receptors (Prochaska and Benowitz 2016). 

Although not FDA-approved for smoking cessation, 

the prescription medications clonidine hydrochloride 

and nortriptyline hydrochloride are recommended as 

second-line agents in the U.S. Public Health Service’s 

Clinical Practice Guideline (Fiore et al. 2008). Lack of an 

FDA-approved indication for smoking cessation, as well as 

some side effects, currently preclude these medications 

from being classified as first-line agents; therefore, they 

are not reviewed in this report. 

To date, seven FDA-approved, first-line medications 

have been found to be safe and effective for treating nicotine dependence—although there are some contraindications for use (e.g., recent myocardial infarction for most 

NRT formulations, seizure disorder for bupropion), as well 

as insufficient evidence of effectiveness and, in some cases, 

safety in certain populations (e.g., pregnant women, light 

smokers, adolescents, and smokeless tobacco users) (Fiore 

et al. 2008). The seven medications include five nicotinebased medications (the nicotine patch, gum, lozenge, nasal 

spray, and oral inhaler) and two non-nicotine oral medications, bupropion and varenicline. Table 6.2 offers in-depth 

information on these seven medications. The nicotine 

patch, gum, and lozenges are available over the counter; 

however, a prescription may still be required for insurance coverage of over-the-counter products. The nicotine 

nasal spray and oral inhaler, bupropion, and varenicline 
NRT formulations

Gum Lozenge Transdermal patch Nasal spray Oral inhaler Bupropion SR Varenicline

Product Nicorette,a ZONNIC,b

Generic

OTC

2 mg, 4 mg original, 

cinnamon, fruit, 

mint

Nicorette Lozenge,a

Nicorette Mini 

Lozenge,a Generic 

OTC

2 mg, 4 mg cherry, 

mint

NicoDerm CQ,a

Generic

OTC (NicoDerm CQ, 

generic)

Rx (generic)

7 mg, 14 mg, 21 mg 

(24-hour release)

Nicotrol NSc

Rx

Metered spray

10 mg/ml aqueous 

solution

Nicotrol Inhalerc

Rx

10-mg cartridge 

delivers 4-mg 

inhaled vapor

Zyban,aGeneric

Rx

150-mg sustainedrelease tablet

Chantixc

Rx

0.5-mg, 1-mg tablet

FDA approval Nicorette:

• 2 mg (Rx) 1984

• 4 mg (Rx) 1991 

ZONNIC:

• 2 mg (OTC) 1996

• 4 mg (OTC) 1996

Lozenge:

• 2 mg (OTC) 2002

• 4 mg (OTC) 2002

Mini-lozenge:

• 2 mg (OTC) 2009

• 4 mg (OTC) 2009

• Rx: 1991–1992

• OTC: 1996–2002

Rx: 1996 Rx: 1997 Rx: 1997 Rx: 2006

A Report of the Surgeon General

510 Chapter 6

Table 6.2 Pharmacologic product guide: FDA-approved medications for smoking cessation
NRT formulations

Gum Lozenge Transdermal patch Nasal spray Oral inhaler Bupropion SR Varenicline

Precautions •

•

•

•

j

•

•

Recent (≤2 weeks) 

myocardial infarction

Serious underlying 

arrhythmias

Serious or worsening 

angina pectoris

Temporomandibular 

oint disease

Pregnancyd and

breastfeeding

Adolescents

(<18 years of age)

•

•

•

•

•

Recent (≤2 weeks) 

myocardial infarction

Serious underlying 

arrhythmias

Serious or worsening 

angina pectoris

Pregnancyd and

breastfeeding

Adolescents

(<18 years of age)

•

•

•

•

•

Recent (≤2 weeks) 

myocardial infarction

Serious underlying 

arrhythmias

Serious or worsening 

angina pectoris

Pregnancyd

(Rx formulations, 

category D) and 

breastfeeding

Adolescents

(<18 years of age)

•

•

•

•

•

•

•

Recent(≤2 weeks) 

myocardial infarction 

Serious underlying 

arrhythmias 

Serious or worsening 

angina pectoris 

Underlying chronic 

nasal disorders 

(rhinitis, nasal polyps, 

sinusitis) 

Severe reactive 

airway disease

Pregnancyd

(categoryD) and 

breastfeeding 

Adolescents 

(<18 years of age) 

•

•

•

•

•

(

•

Recent(≤2 weeks) 

myocardial infarction 

Serious underlying 

arrhythmias 

Serious or worsening 

angina pectoris 

Bronchospastic 

disease 

Pregnancyd

categoryD) and 

breastfeeding 

Adolescents 

(<18 years of age) 

•

•

•

•

•

Concomitant therapy 

with medications/

conditions known

to lower the seizure 

threshold

Hepatic impairment

Pregnancyd

(category C) and 

breastfeeding

Adolescents

(<18 years of age)

Treatment-emergent 

neuropsychiatric 

symptomse: Boxed 

warning removed 

December 2016

Contraindications:

•

•

•

•

•

Seizure disorder

Concomitant 

bupropion (e.g., 

Wellbutrin) therapy

Current or prior 

diagnosis of bulimia 

or anorexia nervosa

Simultaneous abrupt 

discontinuation of 

alcohol or sedatives/

benzodiazepines

MAO inhibitors 

during preceding 

14 days; concurrent 

use of reversible 

MAO inhibitors

•

•

•

•

Severe renal 

impairment (dosage 

adjustment is 

necessary)

Pregnancyd

(category C) and 

breastfeeding

Adolescents

(<18 years of age)

Treatment-emergent 

neuropsychiatric 

symptomse: Boxed 

warning removed 

December 2016

Table 6.2 Continued

Interventions for Smoking Cessation and Treatments for Nicotine Dependence 511
NRT formulations

Gum Lozenge Transdermal patch Nasal spray Oral inhaler Bupropion SR Varenicline

Dosing • 1st cigarette

≤30 minutes after 

waking: 4 mg

• 1st cigarette

>30 minutes after

waking: 2 mg

• Weeks 1–6: 1 piece 

every 1–2 hours

• Weeks 7–9: 1 piece 

every 2–4 hours

• Weeks 10–12: 1 piece 

every 4–8 hours

• Maximum 24 

pieces/day

• Chew each piece 

slowly

• Park between cheek 

and gum when 

peppery or tingling 

sensation appears 

(~15–30 chews)

• Resume chewing 

when tingle fades

• Repeat chew/park 

steps until most of 

the nicotine is gone 

(tingle does not 

return; generally 

30 min)

• Park in different 

areas of mouth

• No food or beverages 

15 minutes before 

or during use

• Duration: up to 

12 weeks

• 1st cigarette

≤30 minutes after 

waking: 4 mg

• 1st cigarette

>30 minutes after

waking: 2 mg

• Weeks 1–6: 1 lozenge 

every 1–2 hours

• Weeks 7–9: 1 lozenge 

every 2–4 hours

• Weeks 10–12:

1 lozenge every

4–8 hours

• Maximum

20 lozenges/day

• Allow to dissolve 

slowly (20–30 minutes for standard;

10 minutes for mini)

• Nicotine release 

may cause a warm, 

tingling sensation

• Do not chew or 

swallow

• Occasionally 

rotate to different 

areas of the mouth

• No food or beverages 

15 minutes before 

or during use

• Duration: up to 

12 weeks

• >10 cigarettes/day:

– 21 mg/day 

for 4–6 weeks

– 14 mg/day 

for 2 weeks

– 7 mg/day for 

2 weeks

• ≤10 cigarettes/day:

– 14 mg/day 

for 6 weeks

– 7 mg/day for 

2 weeks

• Rotate patch 

application site daily; 

do not apply a new 

patch to the same 

skin site for at least 

1 week

• May wear patch 

for 16 hours if

patient experiences 

sleep disturbances 

(remove at bedtime)

• Duration: 

8–10 weeks

• 1–2 doses/hour 

(8–40 doses/day)

• One dose = 2 sprays 

(1 in each nostril); 

each spray delivers

0.5 mg of nicotine to 

the nasal mucosa

• Maximum: 5 doses/

hour or 40 doses/day

• For best results, 

initially use at least 

8 doses/day

• Do not sniff, swallow, 

or inhale through the 

nose as the spray 

is being administered

• Duration: 

3–6 months

• 6–16 cartridges/day

• Individualize 

dosing; initially use 

1 cartridge every 

1–2 hours

• Best effects with 

continuous puffing 

for 20 minutes

• Initially use at least 

6 cartridges/day

• Nicotine in cartridge 

is depleted after

20 minutes of active 

puffing

• Inhale into back 

of throat or puff 

in short breaths

• Do NOT inhale into 

the lungs (like a 

cigarette) but “puff” 

as if lighting a pipe

• Open cartridge 

retains potency 

for 24 hours

• No food or beverages 

15 minutes before 

or during use

• Duration: 

3–6 months

• 150 mg po every 

morning for 3 days, 

then 150 mg po bid

• Do not exceed 

300 mg/day

• Begin therapy 

1–2 weeks prior 

to quit date

• Allow at least 8 hours 

between doses

• Avoid bedtime 

dosing to minimize 

insomnia

• Dose tapering is 

not necessary

• Duration:

7–12 weeks, with 

maintenance up 

to 6 months in 

selected patients

• Days 1–3: 0.5 mg 

po every morning

• Days 4–7: 0.5 mg 

po bid

• Weeks 2–12: 1 mg 

po bid

• Begin therapy 1 week 

prior to quit date

• Take dose after 

eating and with a 

full glass of water

• Dose tapering is 

not necessary

• Dosing adjustment 

is necessary for 

patients with severe 

renal impairment

• Duration: 12 weeks; 

an additional

12-week course 

may be used in 

selected patients

• May initiate up to 

35 days before 

target quit date

• May reduce smoking 

over a 12-week 

period of treatment 

prior to quitting and 

continue treatment 

for an additional

12 weeks

Table 6.2 Continued

A Report of the Surgeon General

512 Chapter 6
NRT formulations

Gum Lozenge Transdermal patch Nasal spray Oral inhaler Bupropion SR Varenicline

Adverse effects •

•

•

•

•

Mouth/jaw soreness

Hiccups

Dyspepsia

Hypersalivation

Effects associated 

with incorrect 

chewing technique:

–

–

–

Lightheadedness

Nausea/vomiting

Throat and mouth 

irritation

•

•

•

•

•

•

•

Nausea

Hiccups

Cough

Heartburn

Headache

Flatulence

Insomnia

•

•

•

Local skin reactions 

(erythema, pruritus, 

burning)

Headache

Sleep disturbances 

(insomnia, abnormal/

vivid dreams); 

associated with 

nocturnal nicotine 

absorption

•

•

•

•

•

•

Nasal and/or 

throat irritation 

(hot, peppery, or 

burning sensation)

Rhinitis

Tearing

Sneezing

Cough

Headache

•

•

•

•

•

•

Mouth and/or 

throat irritation

Cough

Headache

Rhinitis

Dyspepsia

Hiccups

•

•

•

•

•

•

•

•

•

Insomnia

Dry mouth

Nervousness/

difficulty 

concentrating

Nausea

Dizziness

Constipation

Rash

Seizures (risk 

is 0.1%)

Neuropsychiatric 

symptoms (rare; 

see PRECAUTIONS)

•

•

•

•

•

•

Nausea

Sleep disturbances 

(insomnia, abnormal/

vivid dreams)

Constipation

Flatulence

Vomiting

Neuropsychiatric 

symptoms (rare; see 

PRECAUTIONS)

Advantages • Might serve as

an oral substitute 

for tobacco

• Might delay 

weight gain

• Can be titrated to 

manage withdrawal 

symptoms

• Can be used in 

combination with 

other agents to 

manage situational 

urges

• Might serve as

an oral substitute for 

tobacco

• Might delay 

weight gain

• Can be titrated to 

manage withdrawal 

symptoms

• Can be used in 

combination with 

other agents to 

manage situational 

urges

• Once-daily dosing 

associated with fewer 

adherence problems

• Of all NRT products, 

its use is least 

obvious to others

• Can be used in 

combination with 

other agents; 

delivers consistent 

nicotine levels over 

24 hours

• Can be titrated to 

rapidly manage 

withdrawal 

symptoms

• Can be used in 

combination with 

other agents to 

manage situational 

urges

• Might serve as

an oral substitute for 

tobacco

• Can be titrated to 

manage withdrawal 

symptoms

• Mimics hand-tomouth ritual of 

smoking

• Can be used in 

combination with 

other agents to 

manage situational 

urges

• Twice-daily oral 

dosing is simple and 

associated with 

fewer adherence 

problems

• Might delay 

weight gain

• Might be beneficial 

in patients with 

depression

• Can be used in 

combination with 

NRT agents

• Twice-daily oral 

dosing is simple and 

associated with 

fewer adherence 

problems

• Offers a different 

mechanism of 

action for patients 

who have failed 

other agents

Table 6.2 Continued

Interventions for Smoking Cessation and Treatments for Nicotine Dependence 513
NRT formulations

Gum Lozenge Transdermal patch Nasal spray Oral inhaler Bupropion SR Varenicline

Disadvantages •

•

•

•

Need for frequent 

dosing can 

compromise 

adherence

Might be problematic 

for patients with 

significant dental 

work

Proper chewing 

technique is 

necessary for 

effectiveness 

and to minimize 

adverse effects

Gum chewing might 

not be acceptable

or desirable for 

some patients

•

•

Need for frequent 

dosing can 

compromise 

adherence

Gastrointestinal 

side effects 

(nausea, hiccups, 

heartburn) might 

be bothersome

•

•

When used as 

monotherapy, cannot 

be titrated to acutely 

manage withdrawal 

symptoms

Not recommended 

for use by patients 

with dermatologic 

conditions (e.g., 

psoriasis, eczema, 

atopic dermatitis)

•

•

•

Need for frequent 

dosing can 

compromise 

adherence

Nasal administration 

might not be 

acceptable or 

desirable for some 

patients; nasal 

irritation often 

problematic

Not recommended 

for use by patients 

with chronic nasal 

disorders or severe 

reactive airway 

disease

•

•

Need for frequent 

dosing can 

compromise 

adherence

Cartridges might 

be less effective in 

cold environments 

(≤60°F)

•

•

•

Seizure risk is 

increased

Several 

contraindications 

and precautions 

preclude use in 

some patients

(see PRECAUTIONS)

Patients should 

be monitored 

for potential

neuropsychiatric 

symptomse

(see PRECAUTIONS)

•

•

Should be taken 

with food or a full 

glass of water to 

reduce the incidence 

of nausea

Patients should be 

monitored 

for potential

neuropsychiatric 

symptomse

(see PRECAUTIONS)

Cost/dayf 2 mg or 4 mg: $1.90– 

$3.70 (9 pieces)

2 mg or 4 mg: $3.36– 

$3.78 (9 pieces)

$1.52–$3.48

(1 patch)

$6.67

(8 doses)

$11.35

(6 cartridges)

$2.58–$7.87

(2 tablets)

$11.86

(2 tablets)

Table 6.2 Continued

A Report of the Surgeon General

514 Chapter 6

Source: Reproduced with permission from Rx for Change: Clinician-Assisted Tobacco Cessation program. The Regents of the University of California. Copyright © 1999–2017.

Notes: For complete prescribing information and a comprehensive listing of warnings and precautions, please refer to the manufacturers’ package inserts. 

Drug Administration; MAO = monoamine oxidase; mg = milligram; ml = milliliter; NRT = nicotine replacement therapy; 

Rx = prescription product; SR = sustained release.

aMarketed by GlaxoSmithKline.

bMarketed by Niconovum USA (a subsidiary of Reynolds American, Inc.).

cMarketed by Pfizer.

dThe Clinical Practice Guideline (Fiore et al. 2008) states that pregnant smokers should be encouraged to quit without medication based on insufficient evidence of effectiveness and theoretical 

concerns with safety. Pregnant smokers should be offered behavioral counseling interventions that exceed minimal advice to quit.

eIn July 2009, FDA mandated that the prescribing information for all bupropion- and varenicline-containing products include a black-boxed warning highlighting the risk of serious neuropsychiatric 

symptoms, including changes in behavior, hostility, agitation, depressed mood, suicidal thoughts and behavior, and attempted suicide. Clinicians should advise patients to stop taking varenicline or 

bupropion SR and contact a healthcare provider immediately if they experience agitation, depressed mood, or any changes in behavior that are not typical of nicotine withdrawal, or if they experience 

suicidal thoughts or behavior. If treatment is stopped due to neuropsychiatric symptoms, patients should be monitored until the symptoms resolve. Based on results of a mandated clinical trial, 

FDA removed this boxed warning in December 2016.

f

Wholesale acquisition cost from Red Book Online. Thomson Reuters, December 2016.
Interventions for Smoking Cessation and Treatments for Nicotine Dependence 515

Smoking Cessation

are available by prescription only (FDA 2017). The use of 

FDA-approved cessation medications generally doubles 

quit rates relative to placebo, but results vary somewhat 

across products (ORs range from 1.82 for bupropion and 

1.84 for NRTs to 2.88 for varenicline) (Cahill et al. 2013). 

Certain combinations of NRTs have been shown to further 

increase quit rates, including using the transdermal patch 

with any of the other forms of NRT (nicotine gum, lozenges, nasal spray, or inhalers).

The seven cessation medications vary in their mechanisms of action and modes of delivery. Each of the seven 

FDA-approved, first-line cessation medications is described 

below. In addition to a review of these medications and 

combination pharmacotherapy, this section also reviews 

evidence around longer term and pre-quit use of NRT. 

Nicotine Replacement Therapy

NRT delivers nicotine to address physical nicotine 

dependence without exposing the person who is trying to 

quit to the toxic constituents generated by combustion or 

other additives. NRT delivers plasma nicotine concentrations that are lower than those in conventional cigarettes 

and that rise more slowly, thereby reducing the behaviorally reinforcing effect of smoking. Five forms of NRT 

are available in the United States: the transdermal nicotine patch, nicotine gum, nicotine lozenge, nicotine nasal 

spray, and nicotine inhaler; the latter two products are 

available only by prescription (Table 6.2). 

The five forms of NRT are similar in efficacy. Lindson 

and colleagues (2019) observed similar quit rates among 

persons who used a fast-acting form of NRT, such as gum 

or lozenge. Similarly, a meta-analysis of 117 clinical trials 

found that the RR for 6 or more months of abstinence for 

any form of NRT versus controls was 1.60 (95% CI, 1.53–

1.68), with an RR of 1.49 (95% CI, 1.40–1.60) for nicotine 

gum, 1.64 (95% CI, 1.52–1.78) for the nicotine patch, 1.95 

(95% CI, 1.61–2.36) for nicotine lozenges, 2.48 (95% CI, 

1.24–4.94) for the nasal spray, and 1.90 (95% CI, 1.36–

2.67) for the inhaler (Stead et al. 2012). An older randomized study found that medication adherence was lowest for 

the nasal spray and inhaler, moderate for the gum, and 

greatest for the patch; the study did not include the lozenge (Hajek et al. 1999). 

NRT is sold in different dosages (Table  6.2). Some 

healthcare providers recommend higher dosages of NRT 

or combinations of two forms of NRT for more dependent 

smokers, with dependence being defined by the number of 

cigarettes smoked per day or the time to first cigarette after 

awakening (Shiffman et al. 2013). Lindson and colleagues 

(2019) found that, compared with a 2-milligram (mg) dose 

of nicotine gum, using a 4-mg dose increases smokers’ 

chances of successfully stopping smoking. The review also 

found that higher dose nicotine patches appeared to be 

associated with higher rates of abstinence than lower dose 

patches, but this finding was less certain due to the quality 

of the evidence. Nicotine patches, which are applied in 

the morning, deliver nicotine slowly over 16–24  hours 

to achieve a continuous level of nicotine in the blood 

(Wadgave and Nagesh 2016). Several nicotine patches are 

marketed, some of which have tapering dosages (i.e., gradually lowering the dosage over time). The 24-hour patch 

can be removed at bedtime if it causes side effects, such as 

insomnia or bothersome dreams. Oral NRT formulations 

include the nicotine gum, lozenge, and inhaler (Table 6.2). 

The nicotine inhaler is a cigarette-like plastic device that 

delivers nicotine to the throat and upper airway. Nicotine 

in gum and lozenges is primarily absorbed in oral mucosa, 

with a rapid absorption of the nicotine when used properly (Wadgave and Nagesh 2016). However, these oral 

medications are “short acting” and result in relatively low 

levels of nicotine in the blood, initially requiring use every 

1–2 hours to suppress withdrawal symptoms. 

The nicotine nasal spray is administered with one 

spray per nostril; each spray contains 0.5 mg of nicotine 

(Wadgave and Nagesh 2016). The medication can be used 

every 20–60 minutes, with a maximum of 5 doses per hour 

or 40  doses per day. Dosage is based on the number of 

cigarettes smoked per day before starting the medication 

(Pfizer 2010). Of all NRT products, the nasal spray delivers 

nicotine most rapidly, but inhaling cigarette smoke still 

delivers nicotine faster (Wadgave and Nagesh 2016). 

During initial treatment, irritation of the nose commonly 

produces burning, sneezing, and watery eyes; users generally develop tolerance to these effects in 1–2 days (Pfizer 

2010). Other side effects are minor and may include cough 

or headache (Table 6.2); however, NRT use, including longterm use, has been generally found to be safe for most adults 

(Fiore et al. 2008). Some users may opt to start the nasal 

spray a few days before their quit date to work through the 

initial nasal irritation (Wadgave and Nagesh 2016).

Persons with higher levels of nicotine dependence 

are at increased risk for difficulty quitting, abstinence distress, and relapse (Piper et al. 2008). NRT has been shown 

to be particularly effective in highly nicotine-dependent 

smokers (e.g., Stead et al. 2012) relative to smokers with 

lower levels of nicotine dependence and in trials of smoking 

cessation pharmacotherapy in which the majority of participants are at least moderately dependent on nicotine. 

The evidence regarding the efficacy and effectiveness of 

smoking cessation pharmacotherapies focuses mostly on 

highly dependent daily smokers (e.g., Stead et al. 2012). 

Lindson and colleagues (2019) note that there is little 

evidence on the role of NRT for persons smoking fewer 

than 15  cigarettes a day. Evidence supports the efficacy 
A Report of the Surgeon General

516 Chapter 6

of tailoring the dose of NRT to markers of dependence 

(e.g.,  time to first cigarette after waking) (e.g.,  Baker 

et  al. 2007), given that more highly nicotine-dependent 

smokers benefit more from higher doses of NRT than less 

nicotine-dependent smokers (e.g., Stead et al. 2012). 

Bupropion

Bupropion is a prescription medication that blocks 

reuptake of dopamine and, to a lesser extent, norepinephrine. It also has some nicotine receptor-blocking activity 

(Slemmer et al. 2000). Thus, bupropion increases levels 

of dopamine and norepinephrine in the brain, simulating 

nicotine’s effects on these neurotransmitters. In studies 

with rats, bupropion in low doses was found to block nicotine’s rewarding effects, as assessed by the intracranial selfstimulation threshold, and to reverse the negative affective actions of nicotine withdrawal (Cryan et al. 2003). For 

humans, bupropion’s blocking of nicotine receptors could 

contribute to lessened reinforcement from cigarettes in the 

event of a lapse or relapse during a quit attempt (Prochaska 

and Benowitz 2016). Bupropion was originally marketed 

and is still widely used as an antidepressant. However, the 

sustained-release formulation of bupropion was found to 

help smokers quit independent of whether smokers had a 

history of depression (Hurt et al. 1997). Bupropion is initiated 1 week before the scheduled quit date to allow time 

for the smoker to reach steady state therapeutic levels 

(Corelli and Hudmon 2002). In the sustained release formulation, bupropion is started at 150 mg/day. If the initial dose is adequately tolerated, it is increased on day 4 

to 300 mg/day (the recommended maximum daily dose), 

given as two 150-mg doses taken at least 8 hours apart. If 

the 300-mg dose is not well tolerated, the dose is reduced 

to 150 mg/day, which is still efficacious (Swan et al. 2003). 

In a meta-analysis of 65 RCTs of bupropion for 

smoking cessation, Hughes and colleagues (2014) concluded that bupropion alone significantly increased longterm cessation of 6 months or greater (RR = 1.62; 95% CI, 

1.49–1.76) relative to placebo; this level of efficacy was 

comparable to NRT (RR = 0.96; 95% CI, 0.85–1.09) and 

lower than varenicline (RR = 0.68; 95% CI, 0.56–0.83). In 

an RCT conducted in 2001, participants who had quit successfully by week 7 of the trial were randomized to receive 

bupropion or placebo for 1 year to prevent relapse (Hays 

et al. 2001). Bupropion was found to be safe and effective 

and significantly better than placebo at delaying relapse 

(median time to relapse 156 days vs. 65 days, p = 0.021). 

Bupropion also resulted in less weight gain among participants. However, 1 year after treatment, quit rates did 

not differ between the bupropion and placebo groups 

(41.6% vs. 40.0%) (Hays et al. 2001). 

FDA continues to evaluate the safety and effectiveness of cessation medications after they enter the marketplace. Following the introduction of bupropion, the agency 

received and assessed case reports of serious changes in 

mood and behaviors in patients taking bupropion. As a 

result, in 2009 the agency required new boxed warnings 

for bupropion’s product labeling (FDA 2018a). At the time, 

FDA also required the manufacturer to conduct a large 

clinical trial to evaluate the side effects. Based on FDA 

review of the findings from that clinical trial (Anthenelli 

et al. 2016), which is discussed further in the section on 

varenicline, the agency determined the risk of serious side 

effects on mood, behavior, or thinking was lower than previously suspected and determined the product labeling 

should be revised accordingly. FDA noted that while these 

mental health side effects were present, especially in those 

with current or mental illness, they were rare (Anthenelli 

et al. 2016). Additionally, side effects were rarely serious 

enough to result in hospitalization, and the occurrence 

of side effects was no greater for persons randomized to 

bupropion compared with those randomized to nicotine 

patch or placebo.

Varenicline

Varenicline is a prescription medicine marketed specifically for smoking cessation. The drug is a partial agonist of the α4β2 nicotinic acetylcholine receptor subtype, 

which mediates dopamine release and is thought to be the 

major receptor involved in nicotine addiction. Varenicline 

activates the α4β2 nicotinic cholinergic receptor, with a 

maximal effect about 50% that of nicotine, relieving the 

symptoms of nicotine withdrawal, including craving, and 

at the same time blocking the effects of nicotine on the 

receptor, thereby diminishing the rewarding effects of 

cigarettes (Aubin et al. 2014). Thus, the desire to smoke 

and, in the event of a lapse or relapse, the likelihood of 

continued smoking are reduced. As with bupropion, varenicline is initiated 1 week before the quit date (Pfizer 

2018). The dose of varenicline starts at 0.5 mg/day and 

then increases on day 4 to 0.5 mg twice per day and on 

day 7 to 1 mg twice per day (the recommended maximum 

daily dose). This dosing regimen allows for gradual titration of the dose to minimize treatment-related nausea and 

insomnia (Pfizer 2018). The dosage can be lowered temporarily or permanently for patients experiencing intolerable, treatment-associated adverse effects (Pfizer 2018). 

Notably, smokers taking varenicline often reduce their 

smoking even before their target quit day (Ashare et al. 

2012; Ebbert et al. 2015; Nakamura et al. 2017).

The largest clinical trial to date of approved tobacco 

cessation medications, the Evaluating Adverse Events 
Interventions for Smoking Cessation and Treatments for Nicotine Dependence 517

Smoking Cessation

in a Global Smoking Cessation Study (EAGLES), which 

was primarily conducted to examine adverse effects, 

found that (a) varenicline was more effective for quitting 

smoking than placebo, the nicotine patch, or bupropion 

and (b) bupropion and the nicotine patch were more effective than placebo and were comparable to each other in 

efficacy (Anthenelli et al. 2016). This triple-blinded randomized trial enrolled 8,144 daily smokers, about half of 

whom had a stably treated but active psychotic disorder or 

a history of a psychiatric disorder. In the nonpsychiatric 

cohort, continuous abstinence rates (for weeks 9–24) at 

the 6-month follow-up were 25.5% for varenicline, 18.8% 

for bupropion, 18.5% for nicotine patch, and 10.5% for 

placebo. In the psychiatric cohort, continuous abstinence 

rates at the 6-month follow-up were 18.3% for varenicline, 13.7% for bupropion, 13.0% for nicotine patch, and 

8.3% for placebo (Anthenelli et al. 2016). 

Taking varenicline for 6  months has been shown 

to be effective in preventing relapse, including among 

smokers with schizophrenia (Evins et al. 2014). Varenicline 

is FDA-approved for extended (up to 6  months) treatment (Tonstad et al. 2006). Common side effects include 

nausea, vomiting, and insomnia (Cahill et  al. 2013). 

Neuropsychiatric side effects—including depression, psychosis, aggression, and suicidality—have been reported to 

FDA, and the agency required that boxed warning labels 

for both varenicline and bupropion note those possible side 

effects (FDA 2018a). In the EAGLES trial, the primary endpoint was neuropsychiatric safety; the frequency of moderate to severe neuropsychiatric events was less than 3% in 

the nonpsychiatric cohort and less than 7% in the psychiatric cohort, with no significant difference by medication 

condition (Anthenelli et al. 2016). Notably, the findings in 

EAGLES were generally consistent with prior clinical trials 

and observational data. In previous clinical trials of varenicline conducted among smokers with depression and 

schizophrenia, neuropsychiatric side effects had not been 

observed at higher levels relative to those observed in control groups (Williams et  al. 2012; Anthenelli et  al. 2013; 

Cinciripini et al. 2013); this was also the case in large clinical cohort studies (Thomas et al. 2013; Kotz et al. 2015). 

Importantly, smoking itself has been found to be associated 

with mood disturbance, including suicidality (Oquendo 

et al. 2004; Li et al. 2012). Nicotine withdrawal experienced 

during quitting attempts is also characterized by disturbances in mood—including agitation, depressive symptoms, and anxiety—and can cause sleep disturbance with 

associated mood effects (Prochaska and Benowitz 2019).

With regard to the cardiovascular safety of varenicline, an initial meta-analysis raised concerns, showing 

a small but significant RR for serious adverse cardiovascular events compared with placebo (Singh et al. 2011). 

However, a second, larger meta-analysis found the absolute 

risk to be small and statistically nonsignificant (Prochaska 

and Hilton 2012). In addition, a 52-week RCT that examined cardiovascular safety in the EAGLES cohort found no 

significant difference relative to placebo for varenicline, 

bupropion, or nicotine patch on the time to occurrence 

of a major adverse cardiovascular event (Benowitz et al. 

2018). The three time points of interest were during the 

medication treatment period, 30  days post-medication 

use, and at 52 weeks (which marked the end of the study). 

At all three time points, the hazard ratio for major cardiovascular events associated with varenicline was less than 

0.50, which was statistically nonsignificant and suggests 

a reduced risk compared with placebo (Benowitz et  al. 

2018). A biological mechanism by which varenicline could 

produce cardiovascular toxicity has not been identified. 

Additional Approaches to 

Medication Therapy

The seven FDA-approved cessation medications have 

been evaluated in multiple research protocols, with many 

of the study variations aimed at improving our understanding of the reach and short- and long-term efficacy of 

treatment under conditions other than the labeled FDAapproved use. These approaches have included combination pharmacotherapy (i.e., using more than one form of 

medication at a time), pre-loading (starting the medication before the quit date), gradual reduction (using medication as part of an attempt to gradually reduce consumption of tobacco products as a prelude to quitting, instead 

of quitting abruptly), extended treatment (longer use of 

the medication aimed at preventing relapse), and precision medicine (tailoring the medication to differences in 

drug metabolism). The following sections discuss each of 

these approaches in detail.

Combination Pharmacotherapy

Combination pharmacotherapy combines the use 

of cessation drugs that have different mechanisms and/or 

different pharmacokinetic profiles. Dual regimens of NRT 

have generally demonstrated superior efficacy compared 

with a single form of NRT (Ebbert et al. 2010; Tulloch et al. 

2016; Windle et al. 2016). Dual NRT regimens combine the 

use of a transdermal patch, which acts slow and provides a 

base level of nicotine, with any of the other forms of NRT 

(nicotine gum, lozenges, nasal spray, or inhalers)—all of 

which act faster and can be used to offset acute episodes 

of craving or other relapse triggers. Based on evidence 

in their review of 11,356 participants across 14  studies, 

Lindson and colleagues (2019) concluded that combining 

fast-acting forms of NRT with the nicotine patch results in 
A Report of the Surgeon General

518 Chapter 6

long-term quit rates that are higher than those observed 

among persons who use a single form of NRT (RR = 1.25; 

95% CI, 1.15–1.36,). Similarly, in a meta-analysis of nine 

trials, combining the nicotine patch with nicotine gum, 

lozenges, inhalers, or nasal spray was shown to be more 

effective than using individual NRT products (RR = 1.34; 

95% CI, 1.18–1.51) (Stead et al. 2012). A different metaanalysis found that combination NRT had an effect comparable to that of varenicline (OR = 1.06; 95% CI, 0.75–

1.48) (Cahill et al. 2013). 

Emerging evidence also suggests that combining 

varenicline with bupropion or NRT may be more effective 

than taking varenicline alone, particularly among heavier 

smokers (Koegelenberg et  al. 2014; Chang et  al. 2015). 

Two trials examined the combined use of varenicline and 

the nicotine patch. One trial (N  =  435) compared the 

nicotine patch with a placebo patch, both administered 

2 weeks before the target quit date, followed by the addition of varenicline for 1 week before the target quit date; 

the nicotine patch and varenicline were continued for 

12 additional weeks. Use of the nicotine patch plus varenicline resulted in significantly greater quit rates than use of 

the placebo patch plus varenicline at 12 weeks (55.4% vs. 

40.9%, p = 0.007) and 24 weeks (49% vs. 36.2%, p = 0.004) 

(Koegelenberg et  al. 2014). The other trial, which was 

smaller and likely underpowered (N = 117), tested varenicline alone 1  week before the target quit date and then 

with the nicotine patch added at the quit date. The trial 

found statistically nonsignificant differences at 12 weeks 

(38%  vs. 29% quit, p  =  0.14) (Hajek et  al. 2013b). The 

mechanism of benefit from combining varenicline and 

NRT is unclear: varenicline may not fully block α4β2 

receptors or, compared with varenicline alone, the nicotine from NRT may affect additional nicotinic receptors 

that contribute to the addictive effects of nicotine. The 

combination was well tolerated by users in both studies, 

with vivid dreams being the most common side effect 

(Hajek et al. 2013b; Koegelenberg et al. 2014).

In addition, combination therapy with bupropion 

and NRT has been shown to produce better outcomes than 

either medication used by itself (Ebbert et al. 2010). In a 

meta-analysis of eight trials, use of bupropion plus the 

nicotine patch was more effective than use of bupropion 

alone (RR = 1.24; 95% CI, 1.06–1.45) (Stead et al. 2012), 

but a different meta-analysis that reviewed 12 studies in 

which bupropion was added to NRT reported insufficient 

evidence of long-term benefit (at least 6  months) over 

NRT alone (RR = 1.19; 95% CI, 0.94–1.51) (Hughes et al. 

2014). One randomized trial compared the use of bupropion plus varenicline versus the use of varenicline alone 

for 12 weeks (Ebbert et al. 2014); the combination significantly increased continuous abstinence through 12 weeks 

(53.0% vs. 43.2%) and through 26 weeks (36.6% vs. 27.6%) 

but not through 52 weeks (30.9% vs. 24.5%). In a different 

randomized trial, use of bupropion plus varenicline was 

associated with greater depressive symptoms over the first 

2 weeks, but no differences in depressive symptoms were 

observed by week 4 (Hong et al. 2015). 

Pre-Loading Medication

Pre-loading with NRT, or providing NRT in advance 

of a quit attempt, has been tested to see whether it 

increases abstinence rates. The underlying mechanism 

would be to saturate and/or desensitize nicotinic cholinergic receptors to decrease the reward from nicotine 

delivered by smoking. Lindson and colleagues (2019) 

found with a moderate level of certainty that using NRT 

before quitting, instead of using it from the quit date, may 

improve quit rates, but noted that more research is needed 

to confirm this finding. In a meta-analysis of four studies, 

pre-loading with the nicotine patch doubled the odds of 

quitting at 6 weeks (OR = 1.96; 95% CI, 1.31–2.93) and at 

6 months (OR = 2.17; 95% CI, 1.46–3.22) (Shiffman and 

Ferguson 2008). In contrast, a large pragmatic randomized trial in New Zealand in which smokers called a quitline found no boost in abstinence rates when NRT was preloaded, but such pre-loading was determined to be safe, 

acceptable, and easy to implement (Bullen et al. 2010). 

A meta-analysis of eight trials by Stead and colleagues 

(2012) found a moderate but statistically nonsignificant 

effect of pre-loading NRT on abstinence, but effects were 

significant when restricted to the six trials that tested preloading with a nicotine patch. These findings suggest that 

pre-loading in advance of a quit attempt, especially with 

the nicotine patch, can increase abstinence rates. 

Gradual Reduction

Gradually reducing the number of cigarettes smoked 

per day leading up to a quit attempt, rather than quitting all 

at once, may be preferred by smokers who are unwilling to 

quit abruptly (Prochaska and Benowitz 2016). Nationally 

representative data from the 2010–2011 Tobacco Use 

Supplement to the Current Population Survey suggest 

that more than 40% of adult smokers in the United States 

who had tried to quit smoking in the past year reported 

gradually cutting down on their cigarette use as a cessation strategy (Schauer et  al. 2015b). A meta-analysis of 

10 trials evaluating gradual smoking reduction relative to 

quitting abruptly found comparable efficacy, with no difference by treatment approach (e.g., self-help, behavioral, 

pharmacologic) (Lindson-Hawley et al. 2012).

In a different placebo-controlled randomized trial of 

varenicline, Ebbert and colleagues (2015) studied smokers 

who were unwilling to quit in the next month but who were 

willing to reduce smoking immediately and to make a quit 
Interventions for Smoking Cessation and Treatments for Nicotine Dependence 519

Smoking Cessation

attempt within 3 months. Participants received medication 

or placebo for 12 weeks before the quit attempt and were 

advised to reduce the number of cigarettes they smoked 

daily by 50% at 4 weeks, by 75% or more at 8 weeks, and 

then to quit completely at 12 weeks. Varenicline or placebo was continued for an additional 12 weeks after the 

quit date. Quit rates increased approximately threefold in 

the varenicline versus placebo-treated group from week 21 

to 24 (37.8% vs. 12.5%) and from week 21 to 52 (27.0% vs. 

9.9%). Pretreatment with varenicline may reduce craving 

for cigarettes and extinguish the rewarding effects of cigarettes, thus making it easier to quit. Importantly, gradual 

reduction of cigarette consumption should be used only 

as an interim strategy on the path to completely quitting 

smoking, since in the absence of quitting, reduction of 

cigarette consumption alone does not substantially reduce 

health risks (Stead and Lancaster 2007; USDHHS 2014, 

2016; Lindson-Hawley et al. 2016).

Extended Treatment

Currently, NRT package inserts indicate that these 

products should be used for up to 8–12 weeks, depending 

on the type of product. However, studies have explored 

using cessation medications for much longer periods 

(up to 1 year) in an attempt to prevent relapse (Prochaska 

and Benowitz 2016). Similar to chronic disease management approaches, this approach underscores the idea 

that smoking is a chronic, relapsing disease that warrants 

ongoing treatment.

The literature is insufficient, however, to determine 

whether extended NRT is more efficacious than standardduration NRT (Carpenter et  al. 2013). For example, an 

RCT with older smokers found that extended cessation 

treatment—consisting of NRT gum and bupropion for 

12 weeks combined with counseling (group and then individual) extending to 1 year—resulted in abstinence rates 

exceeding 50% at the 2-year follow-up (Hall et al. 2009). 

Notably, the study showed that extending NRT to 52 weeks 

(with no bupropion) did not increase abstinence beyond 

what was achieved with 12 weeks of NRT gum combined 

with bupropion. A trial that assessed point-prevalence 

abstinence in smokers randomized to receive 12 weeks of 

behavioral counseling plus 8, 24, or 52 weeks of nicotine 

patches found that, after 24  weeks of treatment, 21.7% 

of participants in the 8-week arm were abstinent compared with 27.2% (p = 0.17) in the 24- and 52-week arms 

(Schnoll et  al. 2015). Participants in the 52-week arm 

did not report greater abstinence rates than those in the 

24-week arm (20.3% vs. 23.8%, p = 0.57), suggesting that

using NRT beyond 24 weeks may not confer added benefit.

In contrast, varenicline dosed over 6  months has 

been shown to be effective in preventing relapse (Tonstad 

et  al. 2006; Evins et  al. 2014). Currently, FDA labeling 

recommends 12  weeks of therapy, but treatment can be 

extended another 12 weeks if needed. However, patients are 

encouraged to stop sooner if they feel ready. LivingstoneBanks and colleagues (2019) found that with a moderate 

level of certainty, because of unexplained statistical heterogeneity, extended treatment with varenicline helped 

to prevent relapse. In an RCT, Joseph and colleagues 

(2011) tested a chronic care model for smoking cessation. 

Participants in the extended care arm received counseling 

by telephone and NRT for 1 year, and participants in the 

usual care arm received counseling and NRT for 8 weeks. 

At 18 months, the proportion of subjects who were abstinent for 6 months or longer did not differ significantly by 

condition: 30% for extended treatment and 24% (p = 0.13) 

for usual care. Finally, in a meta-analysis of extended 

interventions for preventing relapse, Hajek and colleagues 

(2013c) reported insufficient evidence to support either 

extended cessation counseling or extended pharmacotherapies (NRT, varenicline, or bupropion). More research 

is warranted to continue to assess extended behavioral 

and/or pharmacological treatments for smoking cessation.

Precision Medicine

Precision medicine is an emerging approach to 

smoking cessation treatment (Prochaska and Benowitz 

2016). The goal of precision medicine is to enable clinicians to quickly, efficiently, and accurately predict the 

most appropriate course of action for a patient based on 

genetic and lifestyle factors (Aronson and Rehm 2015). 

Cessation medications are effective in increasing abstinence, but with long-term quit rates rarely surpassing 

30%  (Perkins and Scott 2008), there is great interest 

in identifying differences in response to medications 

to inform personalized treatment, which could potentially increase quit rates. Smokers differ from each other 

in many ways. One is the rate at which they metabolize 

nicotine, which has been studied as a possible basis for 

selecting medications (Prochaska and Benowitz 2016). 

On average, a person who metabolizes nicotine rapidly 

smokes more heavily and appears to be more dependent 

on nicotine than a person who does not metabolize nicotine rapidly (Malaiyandi  et  al. 2005). CYP2A6, a liver 

enzyme, is the chief metabolizer of nicotine; CYP2A6 also 

metabolizes cotinine, the primary metabolite of nicotine, 

which is reduced to 3’-hydroxycotinine (USDHHS 2010). 

The cotinine/3’-hydroxycotinine ratio, also termed 

the nicotine metabolite ratio, can be measured in urine, 

blood, or plasma as a biomarker for the rate at which a 

smoker metabolizes nicotine (USDHHS 2010). In retrospective studies, slow metabolizers received no incremental benefit from bupropion, but they responded well to 

the nicotine patch, while normal metabolizers responded 

better to bupropion than to the patch (Prochaska and 
A Report of the Surgeon General

520 Chapter 6

Benowitz 2016). In a clinical trial that stratified participants by slow or normal nicotine metabolite ratio and 

compared treatment with placebo, the nicotine patch, or 

varenicline (Lerman et al. 2015), slow metabolizers experienced more side effects from varenicline and evidenced 

no benefit in quitting when taking varenicline relative to 

using the nicotine patch (OR = 1.13, p = 0.56), but normal 

metabolizers had greater success with varenicline relative 

to the patch (OR = 2.17, p = 0.001). Thus, use of the nicotine metabolite ratio shows promise in aiding in treatment selection, given that the nicotine patch may be as 

effective as varenicline for slow metabolizers of nicotine, 

while costing less and exposing them to fewer side effects. 

However, use of the nicotine metabolite ratio in clinical 

practice is not yet possible because there is no widely 

available clinical test for this measure. 

Other precision medicine approaches are under 

investigation, including pharmacogenomic variation and 

variance in both behavioral and pharmacologic responses 

between men and women and among persons with certain mental health conditions. For example, pharmacogenomic evidence suggests that variants in gene regions 

that impact dopaminergic neurotransmission, nicotine 

receptor expression, and nicotine and other drug metabolism may predict response to various cessation pharmacotherapies (Chenoweth and Tyndale 2017). Some evidence 

suggests that (a) the superior efficacy of varenicline relative to bupropion and NRT may be greater among women 

than among men and (b) certain mental health conditions 

may also alter responses to behavioral and pharmacological treatments (Luo et al. 2015; McKee et al. 2016; Piper 

et al. 2017; Smith et al. 2017).

Real-World Effectiveness of 

Cessation Medications

In RCTs, the provision of cessation medications 

has consistently increased successful quitting, particularly among heavy cigarette smokers. Several studies 

have reported similar findings in real-world settings 

(West and Zhou 2007; Kasza et al. 2013). For example, the 

International Tobacco Control Four Country Survey found 

increased 6-month continuous abstinence from smoking 

among smokers who reported using varenicline, bupropion, and the nicotine patch but not among those who 

reported using oral NRTs (Kasza et al. 2013). However, some 

population-based studies have found that smokers who used 

NRT (Pierce and Gilpin 2002), and in some cases bupropion 

and varenicline (Leas et al. 2018), reported similar or lower 

rates of quit success compared with those not using these 

medications. These studies have raised questions about the 

real-world effectiveness of these medications, and reviews 

have highlighted conflicting results in the scientific literature (Hughes et al. 2011; Pierce et al. 2012).

Leas and colleagues (2018), using nationally representative data from the 2002–2003 and 2010–2011 waves 

of the Tobacco Use Supplement to the Current Population 

Survey, assessed the effectiveness of cessation medications among adults who smoked at baseline and attempted 

to quit prior to 1 year of follow-up. The study’s authors 

used propensity score matching to control for 12 potential confounders, including smoking intensity, nicotine 

dependence, previous quit history, and self-efficacy to 

quit. The study did not find evidence that the use of varenicline, bupropion, or NRT increases the likelihood of 

smokers being quit for 30 or more days at 1-year followup. Similarly, a study by Kotz and colleagues (2014) conducted in the United Kingdom using cross-sectional data 

from aggregated monthly waves of the Smoking Toolkit 

Study, a household survey, found that smokers who purchased NRT over the counter with no behavioral support 

had similar odds of quitting as smokers who tried to quit 

with no quitting aids.

Several other studies have also found no effects of 

NRT on cessation. For example, a randomized study conducted in New Zealand among 1,410 adult smokers who 

called the national quitline, found that subjects who were 

randomized to receive a free 1-week supply of their choice 

of NRT, followed by a voucher for a free 8-week supply of 

that product, did not have higher rates of abstinence at 

7 days or 6 months compared with those receiving usual 

care from the quitline (Walker et al. 2011). Similarly, a prospective cohort study of a probability sample of 787 adult 

smokers from Massachusetts who had quit smoking found 

that those who quit using NRT were just as likely to 

relapse over the following year as were those who had quit 

without using medications (Alpert et  al. 2013). Finally, 

in a parallel group, factorial design RCT of 2,591 smokers 

16 years of age and older in England, Ferguson and colleagues (2012) found, contrary to findings from multiple 

U.S. randomized trials in quitline settings (An et al. 2006; 

Hollis et al. 2007; Smith et al. 2013), that adding NRT to 

proactive counseling offered through a quitline had no 

additional effect on abstinence. 

Several possible explanations exist for these contradictory findings. Some of the studies that have found 

limited impact of the real-world effectiveness of cessation medications have specific limitations. For example, 

Alpert and colleagues (2013) measured whether prior use 

of NRT had a residual benefit of preventing relapse, which 

differs from assessing whether use of NRT increases cessation success. McAfee (2012) noted several potential 

issues that could have impacted the findings of Ferguson 

and colleagues (2012), including (a) many differences and 

limitations in how NRT was provided in the Ferguson 
Interventions for Smoking Cessation and Treatments for Nicotine Dependence 521

Smoking Cessation

trial compared with U.S. trials that found a positive effect 

(e.g., medications were provided through a voucher that 

had to be redeemed by telephone, adding an extra step for 

participants) and (b) caveats for interpreting the results. 

For example, in a large randomized trial with methods 

similar to those used for the Ferguson trial, which 

involved more than 4,600 U.S. adults who called a quitline, 

overall receipt of study medications was low (43%) compared with the 90% rate at initial intake and the 80% rate 

of medication receipt at 5 weeks. The trial also included 

youth smokers (16–18 years of age), for whom NRT has 

not been found to be effective (Hollis et al. 2007). 

More broadly, most real-world studies have been 

nonrandomized cohort studies that have examined the 

association between self-selected use of cessation medications and quitting success. Without randomization, the study design cannot exclude the potential for 

residual confounding, even with multivariable adjustment. 

Researchers have suggested that conclusions about the 

real-world effectiveness of cessation medications may be 

the result of systematic biases that affect the outcomes of 

cross-sectional surveys (Borland et al. 2012). For example, 

participants may be more likely to recall failed medicationassisted quit attempts than failed unassisted quit attempts. 

Furthermore, smokers who choose to use medications as 

part of a quit attempt may smoke more heavily and be more 

addicted, and therefore may be less likely to succeed, than 

smokers who try to quit without medications. Either of 

these factors could lead to an overrepresentation of failed 

quit attempts among smokers using medications, even if 

these medications actually conferred benefits (Borland 

et  al. 2012). However, Leas and colleagues (2018) used 

propensity score matching on 12 potential confounders, 

including nicotine dependence and smoking intensity, 

and concluded that confounding cannot explain the lack 

of effectiveness of cessation medications in increasing 

long-term cessation in real-world settings.

Another potential factor that could contribute to the 

findings of studies suggesting a lack of real-world effectiveness for cessation medications is the important role 

that behavioral support can play in complementing medication use to maximize cessation, in part by ensuring 

that smokers use cessation medications appropriately and 

effectively (Fiore et al. 2008; USPSTF 2015). While cessation medication and counseling are each effective alone, 

they are more effective when combined (Fiore et al. 2008; 

USPSTF 2015). In particular, providing counseling or decision support to help ensure that consumers use the appropriate medication correctly at the correct dose and for a 

recommended duration, could increase the effectiveness of 

over-the-counter (nonprescription) cessation medications 

in the general population. This type of support is typically 

present in RCTs but is often absent in real-world settings, 

which could explain why many therapies, including cessation medications, might perform more poorly in the real 

world than in clinical trials. The study by Leas and colleagues (2018) supports this hypothesis. Using data from 

the Tobacco Use Supplement to the Current Population 

Survey, they found that only 32 of 186 adult smokers who 

used bupropion and only 9 of 118 smokers who used varenicline as part of a quit attempt, reported receiving any 

form of behavioral counseling. Similarly, Kotz and colleagues (2014) found that smokers who purchased NRT 

over the counter with no behavioral support had similar 

odds of quitting as smokers who tried to quit with no 

quitting aids—also highlighting the important role that 

behavioral support can play in enhancing the effectiveness 

of cessation medications. Further support for this explanation includes the markedly shorter duration of use of medications in real-world settings compared with study settings, averaging 1–2 weeks rather than the recommended 

8–12 weeks (Pierce and Gilpin 2002; Zhang et al. 2015). 

In the absence of behavioral support, tobacco users in 

the general population may not receive adequate information or education about how to use cessation medications 

and what to expect from them (as described previously), or 

they may face barriers to accessing information, including 

such financial barriers as lack of insurance, copays, and 

cost-prohibitive prices (Pacek et al. 2018). Smokers may 

also have misconceptions about the safety of using a medication that contains nicotine (Pierce and Gilpin 2002; Zhang 

et al. 2015). Furthermore, many tobacco users may not be 

aware of changes to the labeling of over-the-counter NRT 

products introduced in 2013, indicating that it is safe to 

use NRT (a) longer than the recommended period, in consultation with a physician if necessary to avoid relapsing, 

and (b) concurrently with smoking (e.g., following a lapse) 

or with another NRT product (Federal Register 2013; FDA 

2013). These and other misconceptions about smoking 

cessation medications could lead people to use them ineffectively, for example, by stopping use prematurely or by 

not using enough of the medication.

Some researchers who have questioned the realworld effectiveness of cessation medications have suggested that an excessive emphasis on the role of medications in helping smokers quit may overmedicalize and 

mystify smoking cessation. They also suggest that such an 

approach may discourage smokers from quitting without 

help (i.e., quitting “cold turkey”), which remains the predominant way that smokers try to quit—and, as a result, 

the predominant way that smokers succeed in quitting—

in the United States (Pierce et al. 2012). In addition, some 

evidence suggests that direct-to-consumer advertisements 

for smoking cessation medications may give smokers a 

false sense of security, suggesting that using these medications will make quitting easy (Frosch et al. 2007). 
A Report of the Surgeon General

522 Chapter 6

Combination Treatment—Behavioral 

Therapy and Pharmacotherapy

Although behavioral therapy and pharmacotherapy 

are each effective interventions for increasing quit rates 

when used alone, combining them is more effective (Fiore 

et al. 2008) and represents the “gold standard” in smoking 

cessation treatment. Use of cessation medications is more 

effective when accompanied by counseling, and use of cessation counseling is more effective when accompanied by 

medications (Fiore et al. 2008). USPSTF (2015) recommends combining medications with multisession, intensive group or individual counseling to achieve the highest 

quit rates; using medication to target physical addiction; and employing behavioral therapy and counseling 

to target psychological and behavioral addiction. A metaanalysis by Stead and colleagues (2016) found that behavioral therapy increased the efficacy of pharmacotherapy 

(RR = 1.27; 95% CI, 1.02–1.58), probably in part because 

it allows healthcare professionals who are delivering the 

behavioral therapy to instruct smokers on using cessation medications properly, managing side effects from the 

medications, understanding and managing cravings and 

withdrawal symptoms, and simultaneously addressing the 

behavioral aspects of tobacco dependence. Similarly, in the 

Smoking Toolkit study from the United Kingdom, Kotz 

and colleagues (2014) found that, compared with smokers 

who used neither cessation medications nor behavioral 

support, those who used prescription cessation medications combined with behavioral support from specialists 

had 3.25 times the adjusted odds (95% CI, 2.05–5.15) of 

remaining abstinent up to the time of the survey; those 

who used prescription cessation medications combined 

with brief advice to quit had 1.61 times the adjusted odds 

(95% CI, 1.33–1.94) of remaining abstinent; and those 

who used NRT purchased over the counter had 0.96 times 

the odds (95% CI, 0.81–1.13) of remaining abstinent. The 

authors concluded that smokers who use a combination of 

behavioral support and cessation medications in their quit 

attempts have almost three times the odds of successfully 

quitting than smokers who use neither. 

Notably, evidence from 40 studies with more 

than 15,000 participants found a significant increase in 

smoking abstinence at 6 months or longer compared with 

controls when pharmacotherapy was added to behavioral 

treatment (RR = 1.82; 95% CI, 1.66–2.00) (Stead and 

Lancaster 2012b; Stead et al. 2016). Earlier, Mottillo and 

colleagues (2009) conducted a meta-analysis of individual, 

group, and telephone counseling in clinical settings from 

50 RCTs (N = 26,927) and found that medications (the 

nicotine patch, bupropion, or nortriptyline) combined 

with counseling led to higher quit rates compared with 

controls. The ORs were similar for individual counseling 

(1.49; 95% CI, 1.08–2.07), group counseling (1.76; 95% CI, 

1.11–2.93), and telephone counseling (1.58; 95% CI, 1.15–

2.29). These results suggest that the highest quit rates are 

achieved through intensive individual or group counseling combined with pharmacotherapy.

Modified and Alternative Tobacco 

Products

Very-Low-Nicotine-Content Cigarettes

Experimental very-low-nicotine-content (VLNC) 

cigarettes (also see Chapter  7) are engineered to have 

reduced content of nicotine in the tobacco used in the cigarette compared with conventionally manufactured cigarettes. The smoke of VLNC cigarettes delivers lower levels 

of nicotine compared with cigarettes that were marketed 

by the tobacco industry in the past as “light” or “ultralight,” which did not have lower levels of nicotine in the 

tobacco itself (Benowitz and Henningfield 2013). Instead, 

light and ultra-light cigarettes relied on design features, 

such as ventilation holes in the filter, to allow these products to be rated as low nicotine (and low tar) when subjected to machine smoking employing a standardized 

method. However, through compensatory behaviors, such 

as blocking ventilation holes with lips and/or fingers, 

drawing larger puffs, and inhaling more deeply, smokers 

were able to obtain levels of nicotine (and tar) that were as 

high as those delivered by conventional (regular strength) 

cigarettes (Benowitz and Henningfield 1994). Scientists 

have suggested that reducing the nicotine content of cigarettes to approximately 0.5  mg per cigarette (compared 

with 10–15 mg per cigarette in most currently marketed 

cigarettes) would render cigarettes nonaddictive. This 

would potentially prevent adolescents from developing 

nicotine addiction and make it easier for adult smokers 

to quit, because cigarettes would be less reinforcing 

(Benowitz and Henningfield 1994). 

Several clinical trials have compared the effects of 

experimental VLNC cigarettes and conventional cigarettes 

on smoking and cessation behaviors. These trials suggest 

that VLNC cigarettes may reduce smoking, reduce nicotine dependence, increase cessation rates, and reduce 

exposure to toxicants (Benowitz et al. 2007, 2012; Donny 

et al. 2007, 2014, 2015; Donny and Jones 2009; Hatsukami 

et al. 2010, 2013, 2018; Dermody et al. 2018). For example, 

Donny and colleagues (2015) and Fiore and Baker (2015) 

conducted a large, multisite clinical trial that randomized 

840 daily smokers to their own cigarettes or to one of six 

variants of study-specific cigarettes with levels of nicotine 

ranging from 0.4 mg of nicotine per gram of tobacco to 
Interventions for Smoking Cessation and Treatments for Nicotine Dependence 523

Smoking Cessation

15.8 mg of nicotine per gram of tobacco (levels typical of 

commercial brands). At 6 weeks, persons assigned to cigarettes with the lowest level of nicotine content smoked 

fewer cigarettes per day and reported less dependence and 

craving than those who smoked regular strength cigarettes 

(i.e., 15.8 mg of nicotine per gram of tobacco). In a randomized, parallel arm, semi-blind study in which 165 smokers 

were randomly assigned to either 0.3  mg nicotine yield 

cigarettes, 0.5 mg nicotine yield cigarettes, or 4 mg nicotine lozenges, Hatsukami and colleagues (2010) found 

that use of 0.5 mg nicotine yield cigarettes was associated 

with reduced carcinogen exposure and reduced nicotine 

dependence and product withdrawal scores, and led to a 

similar rate of cessation to the nicotine lozenge. 

More recently, Hatsukami and colleagues (2018) 

published findings from another large, multisite clinical 

trial that assessed the effects of immediate versus gradual 

reductions in the levels of nicotine content in cigarettes. The authors randomized 1,250 smokers who were 

not interested in quitting into three groups: those who 

(a) continued to smoke conventional cigarettes containing

15.5 mg of nicotine per gram of tobacco; (b) smoked cigarettes in which the level of nicotine content was gradually

reduced over 6 months from 15.5 mg to 0.4 mg of nicotine per gram of tobacco; or (c) switched immediately from

conventional cigarettes to cigarettes with 0.4 mg of nicotine per gram of tobacco and continued to smoke those

cigarettes for 6 months. The study found that smokers who

switched immediately to cigarettes with low levels of nicotine tended to show greater benefits than smokers in the

other two conditions. For instance, compared with gradual

reduction of nicotine, immediate reduction yielded significantly lower levels of biomarkers of exposure to toxic

smoke constituents, a greater reduction in the number of

cigarettes smoked per day, a greater reduction in nicotine

dependence, and more days entirely free of cigarettes. Those 

in the immediate reduction group had significantly lower

levels of breath carbon monoxide compared with those in

the gradual reduction group (difference  =  4.1  parts per

million; 95% CI, -4.89 to -3.23; P <.0055) and with those

in the control group (difference  =  3.4 parts per million;

95% CI, -4.40 to -2.36; P <.0055). Significantly lower levels

in the immediate versus gradual and control groups were

also observed for acrolein (difference  =  17% and 19%,

respectively) and phenanthrene tetraol (difference = 12%

and 14%, respectively). However, for carbon monoxide,

acrolein, and phenanthrene tetraol, there were no significant differences between the gradual reduction and control 

groups. Lower dependence scores (scale ranges from 0 to

10, with higher scores associated with greater dependence)

were observed in (a) the immediate reduction group versus

the gradual reduction group (mean  =  4.27 [low dependence]  vs. 5.13 [moderate dependence]; adjusted mean

difference  =  -0.99 [95%  CI, -1.27  to -0.71]; p  <.00057) 

and (b) the immediate reduction group versus the control 

group (mean = 4.27 [low dependence] vs. 5.48 [moderate 

dependence]; adjusted mean difference  =  -1.44 [95%  CI, 

-1.75 to -1.12]; p <.00057). No differences were found in

the gradual reduction group versus the control group

(mean = 5.13 [moderate dependence] vs. 5.48 [moderate

dependence]; adjusted mean difference  =  -0.45 [95%  CI,

-0.76 to -0.13]; p = .006) (Hatsukami et al. 2018).

However, a study with longer term follow-up reported 

that reducing the nicotine content in cigarettes over 

12 months did not result in sustained reductions in nicotine intake or increases in smoking cessation over the subsequent 12 months (Benowitz et al. 2015). Experimental 

cigarettes were likely less acceptable because conventional 

cigarettes were readily available to the participants in the 

study. The lack of effect of nicotine intake on smoking 

cessation may be the result of compensatory behaviors, 

including consumption of regular-nicotine-content cigarettes. Compensatory smoking (i.e.,  altering smoking 

behaviors to continue to obtain enough nicotine to satisfy 

addiction) has been posited as a possible countervailing 

effect of setting a nicotine product standard (Gottlieb and 

Zeller 2017). However, in its advisory report on a global 

nicotine reduction strategy, which summarized the literature available at that time, WHO (2015) concluded that 

the use of cigarettes with a nicotine content of 0.4 mg/g 

(or less) of cigarette tobacco filler does not significantly 

increase craving or withdrawal and does not result in 

compensatory smoking behaviors. Studies have found 

this to be consistent in populations highly vulnerable to 

nicotine addiction, including individuals with serious 

mental illness (Denlinger-Apte et  al. 2018). However, 

among participants in clinical trials, levels of acceptability 

have been lower for experimental VLNC cigarettes than 

for commercially available cigarettes; and nonadherence 

has been prevalent, with one trial reporting greater than 

70% of participants having substituted traditional cigarette brands for VLNC cigarettes (Nardone et  al. 2016). 

Additionally, 25–45% of participants dropped out of these 

studies (Nardone et al. 2016; Mercincavage et al. 2017).

Combining VLNC cigarettes with nicotine patches 

was hypothesized to perhaps aid with the transition to 

VLNC cigarettes and increase compliance. However, 

Hatsukami and colleagues (2013) did not find that such 

a combination improved long-term quit rates of conventional cigarettes. Furthermore, in a two-by-two factorial 

RCT, Smith and colleagues (2019) found that assignment 

to the patch, along with VLNC cigarettes, did not significantly reduce cigarette smoking compared with assignment to VLNC cigarettes alone (Smith et al. 2019).

If, as outlined by Benowitz and Henningfield (1994, 

2013) and summarized by USDHHS (2014), potential 
A Report of the Surgeon General

524 Chapter 6

“end-game” options to complement existing, proven 

tobacco control interventions include reducing the nicotine content of all cigarettes to make them less addictive, then problems with adherence and attrition would 

not be an issue, unless there was widespread contraband, 

and long-term cessation rates would likely be higher 

than observed in the trials. Because a product standard 

reducing the nicotine content of cigarettes has not yet 

been implemented, studies have not examined the impact 

of a product standard that would reduce the level of nicotine in all cigarettes or other tobacco products would have 

on cessation.

Importantly, the advisory report from WHO (2015) 

noted that the ultimate health benefits of a nicotine 

reduction strategy aimed at individual smokers would 

require that the standard include all combustible tobacco 

products. The WHO report also noted that such a strategy 

needs to be accompanied by the provision of cessation 

treatments to help people quit, including behavioral support and NRT or other medications. In a randomized trial 

comparing the use of experimental VLNC cigarettes with 

the use of cigarettes with conventional levels of nicotine 

over an 8-week period, Hatsukami and colleagues (2017) 

found that smokers in the VLNC cigarette arm (a)  had 

consumed fewer combustible products at almost all 

visits compared with those in the conventional nicotine 

arm (p  <.02); (b)  had higher rates of abstinence (VLNC 

cigarette arm vs. conventional nicotine arm: RR = 9.96; 

95% CI, 5.01–19.81); and (c) used significantly more alternative tobacco products, including nonstudy cigarettes, 

noncigarette combustible products, and noncombustible 

products (RR  =  2.18; 95%  CI, 1.94–2.46 for the VLNC 

cigarette arm  vs. RR  =  1.64; 95%  CI, 1.46–1.85 for the 

conventional nicotine arm). As outlined by WHO (2015), 

for persons who switched from cigarettes to noncombustible forms of tobacco to sustain their nicotine intake, the 

health benefits of not smoking conventional cigarettes 

depended on the level of tobacco-related toxicants delivered by the noncombustible products and the patterns and 

duration of use of such products.

Although evidence to date is suggestive but not sufficient to infer that VLNC cigarettes could reduce smoking 

and nicotine dependence and increase smoking cessation, 

further research could help better understand the impact 

that a nicotine product standard could have on increasing 

cessation from conventional cigarettes. Several issues warrant continued consideration regarding the impacts of a 

nicotine product standard on cigarette cessation, including 

whether compensatory behaviors would occur in the given 

policy framework (Gottlieb and Zeller 2017), whether 

there would be illicit trade for products with higher nicotine yield and how to minimize such effects (Ribisl et al. 

2019), and how populations that are more vulnerable to 

nicotine may be impacted, including those with mental illness and substance use disorders (USDHHS 2016). 

Product standards to decrease nicotine in all 

cigarettes will likely have a greater impact on smoking 

cessation if they are accompanied by a comprehensive cessation strategy that promotes available cessation treatments, including FDA-approved medications and behavioral support.

E-Cigarettes

E-cigarettes (also called electronic nicotine delivery 

systems [ENDS], vapes, vape pens, tanks, mods, and podmods) are battery-powered devices designed to convert a 

liquid (often called e-liquid) into an aerosol for inhalation by the user (Figure 6.1). E-liquid contains solvents 

(propylene glycol and vegetable glycerin) to produce the 

aerosol and typically contains nicotine, flavorings, and 

other compounds. E-cigarettes, which have been available 

in the United States since at least 2007 (USDHHS 2016), 

have been discussed as a potential harm-reduction tool for 

current smokers (Fagerstrom et al. 2015). For this reason, 

smokers, scientists, clinicians, and policymakers have an 

interest in understanding how e-cigarettes will impact the 

smoking cessation landscape.

As e-cigarettes are products designed to deliver nicotine to the body through the pulmonary route, which 

results in more rapid absorption and delivery of nicotine to the brain than through other modes of administration (i.e., mouth, transdermal), it is useful to consider 

their ability to deliver nicotine in the context of a smoker 

attempting to use e-cigarettes to quit cigarette smoking. 

The design and components of many e-cigarettes are 

intended to generate aerosols that can rapidly deliver 

boluses of nicotine to the brain, similar to nicotine 

delivery by conventional cigarettes (Farsalinos et al. 2016). 

E-cigarettes vary in their ability to deliver nicotine to the 

body (Vansickel and Eissenberg 2013). However, the pharmacokinetics of nicotine delivery of certain e-cigarette 

products, such as more recent generation e-cigarettes, 

resemble those of conventional cigarettes, and thus have 

the potential to mirror the pharmacologic effects of conventional cigarettes (National Academies of Sciences, 

Engineering, and Medicine 2018). Therefore, for smokers 

of conventional cigarettes who seek a product with a 

rapid onset of the dose of nicotine similar to cigarettes, 

e-cigarettes that deliver nicotine in a similar way to conventional cigarettes could have greater appeal than current FDA-approved NRTs. However, although rapid boluses 

of nicotine could increase the appeal of these products relative to NRTs, whether this pharmacokinetic profile supports an effective method of cessation has not been extensively studied (Shihadeh and Eissenberg 2015). However, 

when considering e-cigarettes as a potential cessation aid 
Interventions for Smoking Cessation and Treatments for Nicotine Dependence 525

Smoking Cessation

for adult smokers, it is also important to take into account 

factors related to both safety and efficacy. NRT has been 

proven safe and effective, whereas the same has not 

been proven for any e-cigarette. There is no safe tobacco 

product. Although e-cigarette aerosol generally contains 

fewer toxic chemicals than conventional cigarette smoke, 

all tobacco products, including e-cigarettes, carry risks.

Other features of e-cigarettes that may enhance their 

appeal to conventional cigarette smokers are the ways in 

which e-cigarettes mirror some of the sensorimotor features of conventional cigarette smoking, including stimulation of the airways, the sensation and taste of e-cigarette 

aerosol in the mouth and lungs, the hand-to-mouth movements and puffing in which e-cigarette users engage, and 

the exhalation of aerosol that may visually resemble cigarette smoking. Given the potentially important role of 

such sensorimotor factors in the reinforcing and addictive 

qualities of conventional cigarettes (Chaudhri et al. 2006), 

these attributes could make e-cigarettes more appealing to 

smokers than FDA-approved NRTs. However, the sensiromotor aspects of e-cigarettes could (a) facilitate uptake for 

use as a cessation aid, with the goal of attaining complete 

nicotine abstinence, similar to how NRTs are intended to 

be used or (b) facilitate the use of e-cigarettes as a longterm substitute for conventional cigarettes to sustain 

nicotine use. The potential abuse liability of e-cigarettes 

that deliver nicotine in a manner comparable, or higher 

than, conventional cigarettes should also be considered, 

including long-term dual use and decreased likelihood of 

cessation through maintenance of addiction. When considering the potential role of e-cigarettes used in smoking cessation, it is important to consider the intent of therapeutic 

FDA-approved NRT (i.e., that they are intended to act as a 

support for attaining complete abstinence from smoking).

Two previous Surgeon General’s reports have 

addressed e-cigarettes. However, to date, no Surgeon 

General’s report has reviewed the available science related 

to e-cigarettes and cessation. E-cigarettes were first discussed in the 2014 Surgeon General’s report (USDHHS 

2014), which noted that the use of e-cigarettes could 

have positive and negative public health impacts at the 

individual and population levels. Additionally, the 2016 

Surgeon General’s report (USDHHS 2016), E-Cigarette 

Use Among Youth and Young Adults, examined many 

topics related to e-cigarettes, including patterns of use and 

health risks of e-cigarettes among young people, as well 

as the importance of population-based strategies to prevent and reduce the use of e-cigarettes among this population. USDHHS (2016) underscored the need to understand 

any effects of e-cigarettes on adult smoking cessation, 

as well as the risks that the products pose to youth and 

young adults. This is especially important in light of 

alarming increases in e-cigarette use among adolescents, 

which threaten decades of progress in tobacco control 

Figure 6.1 The evolution of e-cigarettes, by product generation and characteristics

Source: Photos by James Gathany and Lauren Bishop, CDC.
A Report of the Surgeon General

526 Chapter 6

(USDHHS 2016; Miech et al. 2018; Gentzke et al. 2019). 

Additionally, e-cigarette, or vaping, product use may be 

associated with other health risks beyond youth initiation 

and use. For example, CDC, FDA, state and local health 

departments, and public health and clinical partners have 

been investigating a multistate outbreak of e-cigarette, 

or  vaping, product use associated lung injury (EVALI) 

(Siegel et al. 2019). The latest national and state findings 

show e-cigarette, or vaping, products containing THC—

particularly those from informal sources, such as friends, 

family, or in-person or online dealers—are linked to most 

of the cases of lung injury and play a major role in the outbreak (Moritz et al. 2019; Navon et al. 2019). In particular, 

vitamin E acetate is closely associated with EVALI (Blount 

et al. 2019). Vitamin E acetate has been identified in several tested products used by EVALI patients, and has been 

identified in bronchoalveolar lavage (BAL) fluid samples 

from 48 of 51 assessed EVALI patients, but not in the BAL 

fluid from a control group. However, as of January 2020, 

evidence is not yet sufficient to rule out the contribution of 

other chemicals of concern among some EVALI patients.

Current use of e-cigarettes among adults rose 

through 2014 (Adkison et al. 2013; Dockrell et al. 2013; 

Goniewicz et  al. 2013; Agaku et  al. 2014; Kasza et  al. 

2017), but has since declined gradually through 2017 

(Wang et al. 2018). In 2017, 2.8% of adults were current 

users of e-cigarettes (Wang et  al. 2018). More than half 

of current adult e-cigarette users also currently smoke 

cigarettes, which is commonly known as “dual use” (CDC 

2016; Mirbolouk et al. 2018). Among current e-cigarette 

users in 2016, 15.0% were never cigarette smokers, 30.4% 

were former smokers, and 54.6% were current smokers 

(Mirbolouk et  al. 2018). Data from the National Youth 

Tobacco Survey showed that among high school students, 

current (past 30-day) e-cigarette use rose from 1.5% in 

2011 to 20.8% in 2018 (Cullen et al. 2018), including a 78% 

increase from 2017 to 2018 (USDHHS 2018a). E-cigarette 

use among middle school students has also risen dramatically in the same time period, with a 49% increase from 

2017 to 2018 (3.3% to 4.9%) (USDHHS 2018a). Dual use 

is also common among youth. In 2018, approximately half 

of youth who used tobacco products reported using two or 

more products; among high school students who reported 

currently using two or more tobacco products, the most 

common combinations reported were e-cigarettes and 

cigarettes (14.8%) (Gentzke et al. 2019).

Since its introduction into the U.S. marketplace 

in 2015, the JUUL brand e-cigarette has been increasingly popular among U.S. youth (USDHHS 2018a), and 

increases in sales in recent years have corresponded with 

the previously described increases in current e-cigarette 

use among U.S. youth in recent years. For example, sales 

of JUUL increased 600% during 2016–2017, largely driven 

by uptake among youth and young adults, giving it the 

greatest market share of any e-cigarette in the United 

States by the end of 2017 (King et al. 2018b). Sales have 

continued to increase since that time; in the assessed 

channels by the end of 2018, JUUL held approximately 75% 

of the market share of total U.S. e-cigarette sales (Truth 

Initiative 2018). JUUL’s popularity with youth appears to 

stem from several factors:

• Appearance of a flash drive,

• Ease of concealment (small and does not emit as much 

aerosol or odor as some other types of e-cigarettes),

• Availability in a variety of flavors, 

• Widespread promotion through a variety of media, 

including social media, and 

• High nicotine content delivered in a form (e.g., nicotine salt) that may facilitate easier initiation (Cullen 

et  al. 2018; Goniewicz et  al. 2018a; Spindle and 

Eissenberg 2018).

E-cigarettes may appeal to adult smokers of conventional cigarettes because they mimic cigarettes in several ways: size, appearance (at least in the case of firstgeneration e-cigarettes), method of inhalation, production 

of a smoke-like aerosol, and the taste and ritual behaviors 

associated with smoking (Prochaska and Benowitz 2016). 

In terms of exposure risks, as part of a comprehensive 

review on the public health consequences of e-cigarette 

use, the National Academies of Sciences, Engineering, 

and Medicine (2018) concluded that for current cigarette 

smokers, completely substituting e-cigarettes for combustible tobacco products would reduce exposure to several 

toxicants and carcinogens present in tobacco cigarettes. 

For example, an analysis of 12 first-generation brands of 

e-cigarettes found that toxicants (including carcinogenic 

compounds) were present in the e-cigarettes’ aerosol 

across brands at varying levels, ranging from about 9- to 

450-times lower than cigarette smoke to levels in some 

brands that were comparable to levels in the NRT inhaler 

(Goniewicz et  al. 2014). In a separate analysis of urine 

samples from 5,105 adult participants in the 2013–2014 

wave of the Population Assessment of Tobacco and Health 

(PATH) Study, Goniewicz and colleagues (2018b) concluded that the exclusive use of e-cigarettes was associated with exposure to known tobacco-related toxicants 

(e.g.,  tobacco-specific nitrosamines, such metals as cadmium and lead, and some volatile organic compounds), 

but that this exposure was markedly lower than that 

associated with both cigarette smoking and dual use of 
Interventions for Smoking Cessation and Treatments for Nicotine Dependence 527

Smoking Cessation

cigarettes and e-cigarettes. However, depending on the 

toxicant analyzed, dual users (n  =  792) had similar or 

higher exposures to toxicants compared with users of only 

conventional cigarettes (n  =  2,411). Among dual users, 

the frequency of cigarette use was positively correlated 

with exposure to both nicotine and toxicants. These findings suggest that exclusive use of e-cigarettes can result 

in markedly lower exposure to tobacco-related toxicants 

compared with exclusive use of conventional cigarettes, 

but that using e-cigarettes concurrently with conventional cigarettes does not meaningfully reduce exposure to 

potentially harmful toxicants. Of note, ingredients unique 

to e-cigarettes (i.e., not found in conventional cigarettes) 

pose potential harms (Erythropel et al. 2019). It is important to note that the findings from the PATH Study analysis pertain to e-cigarette products used in 2013–2014, and 

because the landscape of e-cigarette products continues 

to diversify and evolve rapidly, the findings may or may 

not be generalizable to behaviors surrounding the use of 

these products years later (e.g.,  in 2019). Moreover, the 

National Academies of Science Engineering and Medicine 

(2018) concluded that exposure to nicotine and exposure 

to potentially toxic substances in aerosol from e-cigarettes 

are highly variable and depend on product characteristics 

(e.g., e-liquid constituents and device characteristics and 

settings), how the device is operated, and user behavior.

Although the available scientific evidence indicates that e-cigarettes generally have a markedly lower 

number and level of harmful toxicants than conventional 

cigarettes, use of the products is not without potential 

health risks; the long-term health effects of using these 

products remain unknown, and short-term risks are only 

slowly coming into focus (National Academies of Sciences, 

Engineering, and Medicine 2018). However, the National 

Academies of Sciences, Engineering, and Medicine (2018) 

concluded that there is substantial evidence that e-cigarette 

use is associated with several adverse health outcomes that 

are precursors to disease, including acute endothelial cell 

dysfunction, formation of reactive oxygen species/oxidative stress, and increased heart rate (National Academies 

of Sciences, Engineering, and Medicine 2018). The report 

also concluded that there is substantial evidence that some 

chemicals present in e-cigarette aerosols are capable of 

causing DNA damage and mutagenesis, which supports the 

biologic plausibility that long-term exposure to e-cigarette 

aerosols could increase risk of cancer and adverse reproductive outcomes; however, whether the levels of exposure 

are high enough to contribute to human carcinogenesis 

remains uncertain. The report further noted that there 

is no available evidence whether e-cigarette use is associated with certain longer term health outcomes, including 

clinical cardiovascular outcomes and subclinical atherosclerosis, intermediate cancer endpoints in humans, 

respiratory diseases, and pregnancy outcomes (National 

Academies of Sciences, Engineering, and Medicine 2018). 

Additionally, Gotts and colleagues (2019) reviewed the 

available science to date on risks to the respiratory system 

from using e-cigarettes or being exposed to aerosol from 

e-cigarettes. The study found negative impacts on cellular and organ physiology and immune function (Gotts

et  al. 2019). Accordingly, more research is warranted to

assess the extent to which e-cigarette use may impact the

likelihood of these and other health outcomes. Of note,

some studies have found that after accounting for conventional cigarette smoking, e-cigarette use is associated

with increased risk of having had a myocardial infarction

(Alzahrani et  al. 2018; Alzahrani and Glantz 2019; Osei

et al. 2019). However, the cross-sectional nature of these

studies limits the ability to ascertain causality (Farsalinos

and Niaura 2019a). A longitudinal study using data from

the PATH Study found that having had a myocardial infarction at Wave 1 of the study did not predict e-cigarette use at 

Wave 2 (Bhatta and Glantz 2019). This finding, according

to the study’s authors, suggests that reverse causality

cannot explain the cross-sectional association between

e-cigarette use and myocardial infarction observed at

Wave  1. However, further longitudinal research is warranted to fully account for the time period when myocardial infarction has occurred relative to e-cigarette use.

Research on the impact of e-cigarettes on smoking 

cessation is limited but growing. In addition to the review 

of this topic by the National Academies of Sciences, 

Engineering, and Medicine (2018), multiple systematic 

reviews have assessed the literature on e-cigarette use and 

smoking cessation, some of which conducted meta-analyses 

of RCT data and observational studies (Franck et al. 2014; 

Grana et al. 2014; Harrell et al. 2014; McRobbie et al. 2014; 

Lam and West 2015; Rahman et al. 2015; Hartmann-Boyce 

et al. 2016; Kalkhoran and Glantz 2016; Khoudigian et al. 

2016; Malas et al. 2016; El Dib et al. 2017).

Few RCTs have been conducted that directly investigate the utility of e-cigarettes for smoking cessation, 

and no RCTs on this topic have been conducted in the 

United States. Only four RCTs—a clinical trial of smokers 

in Italy who were not motivated to quit (Caponnetto et al. 

2013), a clinical trial of smokers in New Zealand who were 

motivated to quit (Bullen et  al. 2013), another clinical 

trial of smokers in New Zealand who were motivated to 

quit (Walker et al. 2019), and an RCT of adults using the 

stop-smoking service of the UK National Health Service 

(Hajek et  al. 2019)—have directly tested the efficacy of 

using e-cigarettes for smoking cessation with a followup timepoint of at least 6 months; none were funded by 

the tobacco or e-cigarette industries. In a randomized 

clinical trial of smokers who were not motivated to quit, 

Caponnetto and colleagues (2013) found that the use of 
A Report of the Surgeon General

528 Chapter 6

first-generation e-cigarettes resulted in a nonsignificant 

(p = 0.24) increase in the likelihood of smoking abstinence 

at 52-weeks follow-up compared with those who used firstgeneration e-cigarettes that did not contain nicotine (placebo e-cigarette). Abstinence rates were 13% in Group A 

(12-weeks supply of 7.2  mg nicotine cartridges), 9% in 

Group B (one 6-week supply of 7.2-mg nicotine cartridges 

and one 6-week supply of 5.4-mg nicotine cartridges), and 

4% in Group  C (cartridges without nicotine). However, 

in an intention-to-treat analysis, a statistically significant 

increase in the abstinence rate was observed at 52-weeks 

follow-up: 11.0% when Groups  A and  B were combined 

compared with 4.0% in Group C (p = 0.04). The RCT by 

Bullen and colleagues (2013) also showed (a) a nonsignificant elevated RR of 6-month continuous abstinence rates 

for smokers who were assigned to use first generation 

e-cigarettes that contained nicotine compared with those 

who were assigned to use first generation e-cigarettes that 

did not contain nicotine (7.3% vs 4.1%, RR 1.77, p = 0.44) 

and (b) a nonsignificantly elevated RR for 6-month continuous abstinence (RR = 1.26; p = 0.46) between smokers 

who were assigned to use e-cigarettes that contained nicotine (7.3%) and those who were assigned to use nicotine patches (5.8%). As reviewed in National Academies of 

Sciences, Engineering, and Medicine (2018), the results 

of these two RCTs were pooled in two different, rigorous 

meta-analyses. A 2016 Cochrane review that pooled data 

from these two RCTs showed (a) no significant statistical 

heterogeneity between the two studies and (b) that use of 

nicotine-containing e-cigarettes was associated with statistically significant higher abstinence rates than use of placebo e-cigarettes (RR = 2.29; 95% CI, 1.05–4.96; 9% for nicotine e-cigarette group vs. 4% in placebo e-cigarette group, 

among 662  participants) (Hartmann-Boyce et  al. 2016). 

El Dib and colleagues (2017) pooled the same two RCTs 

into a meta-analysis and found a nonsignificant increase 

in smoking cessation for nicotine e-cigarettes compared 

with placebo e-cigarettes (RR = 2.03; 95% CI, 0.94–4.38; 

p = 0.07). A notable difference in the methodology between 

these two reviews was that Hartmann-Boyce and colleagues (2016) considered participants with missing data 

as smokers and retained them in the analysis, increasing 

their sample size to 662 compared with the 481 cases analyzed by El Dib and colleagues (2017) (National Academies 

of Sciences, Engineering, and Medicine 2018).

A few notable limitations to two RCTs (Bullen et al. 

2013; Caponnetto et al. 2013) should be noted: They both 

produced fairly low quit rates in all conditions (range: 

4–13%) and used first generation e-cigarettes that do 

not have comparable nicotine pharmacokinetics as cigarettes. Furthermore, Bullen and colleagues (2013) found 

that rates of compliance were substantially lower among 

smokers in the nicotine patch condition than among 

those in either of the e-cigarette conditions, suggesting 

that the similar efficacy among users of e-cigarettes with 

nicotine and of the nicotine patches might be mediated 

by different mechanisms of action. The greater adherence 

to e-cigarettes could be driven, in part, by past experience 

of failed quit attempts with patches and/or greater appeal 

of e-cigarettes.

The third RCT (Hajek et al. 2019) randomly assigned 

886 adults attending stop-smoking services from the UK 

National Health Service. Participants received either an 

NRT medication of their choice or an e-cigarette starter 

pack, which included a newer generation refillable 

e-cigarette with one bottle of nicotine e-liquid (18  mg 

per milliliter [ml]). Both conditions received face-toface smoking cessation counseling from a trained counselor for at least 4  weeks. At 1  year, the biochemically 

verified cigarette smoking abstinence rate was 18.0% in 

the e-cigarette group compared with 9.9% in the NRT 

group. Of note, participants in both the e-cigarette and 

NRT groups rated their assigned products as less satisfying than cigarettes. However, participants who were 

assigned to use e-cigarettes reported that e-cigarettes provided them with greater satisfaction and rated e-cigarettes 

as more helpful to refrain from smoking than participants in the NRT group rated NRT medications (Hajek 

et al. 2019). The study concluded that use of e-cigarettes 

was more effective than use of NRT for smoking cessation in the trial when both were accompanied by behavioral support. Of  note, among participants with 1-year 

abstinence, 80% of participants in the e-cigarette group 

were using e-cigarettes at 52  weeks follow-up and 9% 

of participants in the NRT group were using NRT, suggesting greater likelihood of complete abstinence from all 

products in the long term from NRT use compared with 

e-cigarette use. This also suggests that, among those who 

use e-cigarettes for smoking cessation, cigarette abstinence may be predicated on long-term use of e-cigarettes, 

which may pose unknown long-term health risks, in addition to short-term risks that are only slowly coming into 

focus. Limitations of the study should also be considered. 

First, participants were enrolled through the UK National 

Health Service’s stop-smoking service, so they were motivated to quit. Participants also received evidence-based 

cessation counseling in addition to e-cigarettes or NRT. 

Furthermore, the policy and regulatory environment 

regarding both e-cigarettes and tobacco products in the 

United Kingdom differs greatly from that of the United 

States. For example, compared with the United States, the 

United Kingdom limits the amount of nicotine permitted 

in e-cigarettes (maximum concentration 20 mg/ml) and 

has more restrictions on the advertising and marketing 

of e-cigarettes, which aligns with its advertising restrictions on tobacco products more generally. Further 
Interventions for Smoking Cessation and Treatments for Nicotine Dependence 529

Smoking Cessation

well-designed RCTs will ultimately be important before 

any substantive conclusions can be made about the comparative efficacy of e-cigarettes relative to NRT, other cessation pharmacotherapies, or not using a cessation aid. 

A fourth RCT conducted in 2016–2017 in New 

Zealand explored e-cigarettes, with and without nicotine, as an adjunct to the nicotine patch (Walker et  al. 

2019). The study randomized smokers motivated to quit 

(n = 1,124) to receive either nicotine patch, nicotine patch 

plus nicotine-containing e-cigarettes, or nicotine patch 

plus nicotine-free e-cigarettes. Participants randomized to 

the e-cigarette conditions received a tank-style device and 

tobacco-flavored e-liquid in either 0 mg/ml or 18 mg/ml 

concentration, depending on assigned group; and all participants received 21 mg nicotine patches. Smokers using 

nicotine-containing e-cigarettes were more likely to have 

biochemically verified, continuous cigarette abstinence 

at 6-month follow-up than those randomized to patch 

plus nicotine-free e-cigarettes or to nicotine patch alone 

(7%, 4%, and 2%, respectively). However, the study had 

higher than expected rates of attrition: 50% in the patchonly group, 32% in the patch plus nicotine-containing 

e-cigarettes group, and 33% in the patch plus nicotinefree e-cigarettes group. Moreover, quit rates were much 

lower than expected among all three randomized groups. 

In addition to the aforementioned RCTs, an additional RCT assigned smokers employed by 54 companies 

to one of four workplace smoking-cessation interventions or to usual care (Halpern et  al. 2018). Usual care 

consisted of access to information about the benefits of 

smoking cessation and to a motivational text-messaging 

service. The four interventions consisted of usual care and 

one of the following interventions: free access to cessation 

aids (NRT or pharmacotherapy, with e-cigarettes if standard therapies failed); free access to e-cigarettes, without 

a requirement that standard therapies had been tried; free 

access to cessation aids and $600 in rewards for sustained 

abstinence; or free access to cessation aids plus $600 in 

redeemable funds, with money removed from the account 

if cessation milestones were not met. The study found that 

rates of sustained abstinence through 6 months were 0.1% 

in the usual care group, 0.5% in the free cessation aids 

group, 1.0% in the free e-cigarettes group, 2.0% in the 

rewards group, and 2.9% in the redeemable funds group. 

Of note, the free e-cigarettes intervention was not superior 

to usual care (p = 0.20) or to the free cessation aids intervention (p = 0.43), and among smokers who received usual 

care, the addition of free cessation aids or e-cigarettes did 

not significantly enhance cessation efficacy. However, 

the study did not assess actual use of e-cigarettes, only 

access to the products, nor did it compare free access to 

e-cigarettes with free access to conventional cessation aids 

without any option for e-cigarettes (Halpern et al. 2018).

In addition to the data from the previously summarized RCTs, multiple observational studies have explored 

the effectiveness of using e-cigarettes for smoking cessation. Several systematic reviews have synthesized the 

observational literature on the impact of e-cigarette use 

on smoking cessation (Franck et  al. 2014; Grana et  al. 

2014; Harrell et al. 2014; McRobbie et al. 2014; Lam and 

West 2015; Rahman et  al. 2015; Hartmann-Boyce et  al. 

2016; Kalkhoran and Glantz 2016; Khoudigian et al. 2016; 

Malas et al. 2016; El Dib et al. 2017). The review by El Dib 

and colleagues (2017), which used a methodology known 

as GRADE (Grading of Recommendations Assessment, 

Development, and Evaluation) to formally assess the certainty of evidence by outcome, concluded that the findings on this topic from two RCTs (Bullen et  al. 2013; 

Caponnetto et  al. 2013) and eight observational studies 

(Vickerman et al. 2013; Borderud et al. 2014; Prochaska and 

Grana 2014; Al-Delaimy et al. 2015; Biener and Hargraves 

2015; Brose et al. 2015; Harrington et al. 2015; Manzoli 

et al. 2015) were of very low quality. Several of the reviews 

noted that findings from the observational studies varied, 

and differences in study design and the selection of participants made it difficult to make conclusive comparisons. 

Similarly, a review conducted by USPSTF (2015), which 

also considered the existing RCTs, concluded that the current evidence was insufficient to recommend e-cigarettes 

for tobacco cessation in adults, including pregnant women.

In one of the prospective observational studies, 

Manzoli and colleagues (2015) reported that the rate of 

quitting smoking did not differ between smokers who 

had used e-cigarettes weekly for at least 6  months and 

smokers who did not use e-cigarettes. However, in a longitudinal study of a nationally representative population 

of adults surveyed in 2012 and 2014, Zhuang and colleagues (2016) found that long-term e-cigarette users 

appeared to have (a)  higher rates of quit attempts than 

short-term e-cigarette users or nonusers of e-cigarettes 

(72.6% vs. 53.8% and 45.5%, respectively) and (b) higher 

rates of cigarette cessation (42.4% vs. 14.2% and 15.6%, 

respectively). Adjusting for smoking characteristics and 

demographics, long-term e-cigarette users were significantly more likely than nonusers of e-cigarettes to try to 

quit smoking (OR = 2.94; 95% CI, 1.34–6.44) and to do so 

successfully (OR  =  4.14; 95%  CI, 1.50–11.42); cessation 

outcomes for short-term e-cigarette users were similar to 

those for nonusers. The study also found that 43.7% of 

adults who were dual users of cigarettes and e-cigarettes 

at baseline were still using e-cigarettes at follow-up. 

In a study of multiple years of nationally representative 

data from the U.S. Current Population Survey Tobacco 

Use Supplement, Zhu and colleagues (2017) found that 

the smoking cessation rate for the overall population 

increased from 4.5% in 2010–2011 to 5.6% in 2014–2015, 
A Report of the Surgeon General

530 Chapter 6

and in 2014–2015, e-cigarette users were more likely than 

nonusers to attempt to quit smoking (65.1% vs. 40.1%; 

percentage point change  =  25%; 95%  CI, 23.2–26.9%) 

and to succeed in quitting (8.2%  vs. 4.8%, p  <0.001). 

The study also examined the potential impact on cessation of other tobacco control efforts that were underway 

during the study period (e.g., mass media campaigns and 

increased taxation of cigarettes) and concluded that their 

effects could not fully account for the observed increase 

in the quit rate, leaving the use of e-cigarettes as a potential explanation. Finally, in a cross-sectional household 

survey of smokers 16 years of age and older in England, 

Beard and colleagues (2016) found that the success rate of 

attempts to quit cigarettes increased by 0.098% (p <.001) 

for every 1% increase in the prevalence of e-cigarette use 

among smokers, and by 0.058% for every 1% increase 

in the prevalence of e-cigarette use during a recent quit 

attempt. The study concluded that increases in e-cigarette 

use in England have been associated with increased success in quitting cigarette smoking. 

As noted previously, some of the literature suggests potential utility of e-cigarettes for smoking cessation. However, the current literature is limited by small 

numbers of trials, low event rates, and wide confidence 

intervals. Moreover, interpretation of results is further 

complicated by the wide variation in e-cigarette products 

(i.e., types of devices and components and levels of nicotine content in e-liquids) and the contexts in which they 

are used, including the motivation of smokers to quit and 

whether the products are used with behavioral support. 

Accordingly, more well-designed RCTs and prospective 

observational studies are needed to determine whether 

and how e-cigarettes influence smoking cessation, 

including whether the type of e-cigarette and the setting 

in which it is used impacts the potential for e-cigarette use 

to help smokers quit. 

Existing research suggests that the frequency of 

e-cigarette use and the type of product are important 

factors that influence the extent to which the products 

increase the likelihood of smoking cessation. As part of a 

comprehensive report on the public health consequences 

of e-cigarettes, the National Academies of Sciences, 

Engineering, and Medicine (2018) reviewed three RCTs 

(Bullen et al. 2013; Caponnetto et al. 2013; Adriaens et al. 

2014)—one of which assessed smoking reduction and 

not actual cessation (Adriaens et  al. 2014)—and results 

from several prospective cohort studies or repeated crosssectional design studies (Biener and Hargraves 2015; Brose 

et  al. 2015; Hitchman et  al. 2015; Delnevo et  al. 2016; 

Malas et  al. 2016; Zhuang et  al. 2016; Levy et  al. 2018) 

on the effectiveness of e-cigarettes for smoking cessation. 

The review concluded that while the overall evidence from 

observational trials is mixed, there is moderate evidence 

from observational studies that more frequent use of 

e-cigarettes is associated with an increased likelihood of 

cessation. For example, in a cross-sectional study using 

data from the 2016 and 2017 National Health Interview 

Survey, Farsalinos and Niaura (2019b) found that daily 

e-cigarette use was not associated with being a former 

smoker when quit duration was ignored, but was positively associated with being a former smoker of less than 

1  year (adjusted prevalence ratio [aPR]  =  3.44; 95%  CI, 

2.63–4.49), 1–3  years (aPR  =  2.51; 95%  CI, 2.13–2.95), 

and 4–6 years (aPR = 1.84; 95% CI, 1.49–2.26). Moreover, 

using data from waves 1 (2013–2014) and 2 (2014–2015) of 

the Population Assessment of Tobacco and Health Study, 

Berry and colleagues (2019) found that after adjusting for 

covariates, (a) cigarette smokers who initiated e-cigarette 

use between waves and reported that they used e-cigarettes 

daily at wave 2, had 7.88 (95% CI, 4.45–13.95) times the 

odds of 30-day cigarette cessation compared with nonusers 

of e-cigarettes at wave 2, and (b) nondaily e-cigarette users 

had significantly lower odds of cessation compared with 

nonusers. Similarly, in a longitudinal sample from two 

U.S. municipalities, Biener and Hargraves (2015) found 

that after accounting for demographic characteristics and 

tobacco dependence, intensive users of e-cigarettes (used 

e-cigarettes daily for at least 1 month) were six times more 

likely than nonusers to quit smoking (OR = 6.07; 95% CI, 

1.11–33.2); a comparable relationship was not observed 

between intermittent users (used e-cigarettes regularly 

but not daily for more than 1 month) and nonusers/triers 

(used e-cigarettes only once or twice). Furthermore, 

among a longitudinal sample of smokers in Great Britain, 

Hitchman and colleagues (2015) found that compared with 

smokers who did not report using e-cigarettes at followup, nondaily users of disposable e-cigarettes were less 

likely to have quit smoking since baseline (p = 0.0002); 

daily users of disposable e-cigarettes and nondaily users 

of tank-style e-cigarettes were no more or less likely to 

have quit (p = 0.36 and p = 0.42, respectively); and daily 

users of tank-style e-cigarettes were more likely to have 

quit (p ≤0.01). These findings are consistent with findings 

from the RCT by Hajek and colleagues (2019), which found 

greater efficacy for cessation from the use of more recent 

generations of e-cigarettes with higher nicotine yield, and 

from studies showing that open tank e-cigarettes, which 

allow the user to refill the nicotine liquid and to titrate 

the dose of nicotine, result in greater nicotine absorption 

(Farsalinos et al. 2013a,b; 2015). Most recently, Gomajee 

and colleagues (2019) assessed longitudinal data from 

the CONSTANCES (Consultants des Centres d’Examens 

de Santé) cohort and found that among the 5,400  daily 

smokers, daily e-cigarette use was associated with a significantly higher decrease in the number of cigarettes 

smoked per day compared with daily smokers who did 
Interventions for Smoking Cessation and Treatments for Nicotine Dependence 531

Smoking Cessation

not use e-cigarettes (-4.4  [95%  CI, -4.8  to -3.9]  vs. -2.7 

[95% CI, -3.1 to -2.4]), as well as a higher adjusted RR of 

smoking cessation (1.67; 95%  CI, 1.51–1.84]). However, 

among 2,025  former smokers, e-cigarette use was associated with an increase in the rate of smoking relapse 

(adjusted hazard ratio  =  1.70; 95%  CI, 1.25–2.30) compared with former smokers who did not use e-cigarettes. 

In addition to frequency of use and product type, some 

data suggest that the reason for using e-cigarettes (e.g., to 

quit or reduce smoking  vs. all other reasons) may be 

an important factor that influences the effectiveness of 

e-cigarettes for smoking cessation (Vickerman et al. 2017). 

Taken together, these findings suggest that the type and

design of e-cigarettes (e.g., open tank systems vs. closed

systems vs. disposable) and the way in which they are used

(e.g., more frequent use vs. less frequent use) may affect

their utility for cessation (Hitchman et al. 2015).

The landscape of e-cigarettes continues to evolve, 

with the arrival of a new generation of devices and e-liquids 

that can more efficiently deliver nicotine (Farsalinos et al. 

2014; USDHHS 2018b). For example, some e-cigarettes 

contain nicotine salt e-liquids (also called nic salts); nicotine salts are created by adding an acid to the nicotine 

to lower the overall pH (Goniewicz et al. 2018a; Spindle 

and Eissenberg 2018). Nicotine salt-based liquids allow 

users to inhale aerosols with high levels of nicotine more 

easily and with less irritation than the freebase nicotine 

e-liquids that have been used in e-cigarettes since they

were first introduced into the marketplace (USDHHS

2018b; O’Connell et  al. 2019). Nicotine salt e-liquids

may also help deliver nicotine to the brain faster and in

a way that is more comparable to the nicotine delivery

achieved via conventional cigarettes (Goniewicz et  al.

2018a). Although justifiable concerns exist that nicotine

salts could promote initiation of e-cigarette use among

youth, this new product formulation also has the potential to enhance the dose and efficiency with which nicotine is delivered to adult smokers who may be attempting

to quit smoking, thus potentially increasing the likelihood

that they are able to transition completely to e-cigarettes.

However, this formulation could also make it more difficult for those who fully transition to e-cigarettes to eventually quit using these products completely.

The 2014 Surgeon General’s report noted that “the 

promotion of noncombustible products is much more 

likely to provide public health benefits only in an environment where the appeal, accessibility, promotion, and use 

of cigarettes and other combusted tobacco products are 

being rapidly reduced” (USDHHS 2014, p. 874). Therefore, 

it is particularly important to consider both the potential 

benefits of e-cigarettes for smoking cessation and the high 

level of e-cigarette use among youth, which increased to 

unprecedented levels between 2017 and 2018 primarily 

because of the introduction of JUUL and other e-cigarettes 

shaped like USB flash drives (Cullen et al. 2018). As noted 

by the National Academies of Sciences, Engineering, and 

Medicine (2018), the specific time frame and magnitude 

of population health effects of e-cigarettes will depend on 

their impact on the rates of initiation and net cessation of 

combustible tobacco cigarettes and their intrinsic harm, 

and the risks of the high level of e-cigarette use among 

youth. To date, a variety of modeling projections have estimated the potential magnitude of these effects, but it is 

important to note that results can vary greatly depending 

on parameter inputs, underlying assumptions, and other 

factors. Using a Mendez-Warner modeling approach, the 

National Academies of Sciences, Engineering, and Medicine 

(2018) found that the use of e-cigarettes will generate a net 

public health benefit, at least in the short term. The model 

found that the harms from increased initiation by youth 

will take time to manifest, occurring decades after the 

benefits of increased cessation are observed. However, for 

long-term projections, the net public health benefit was 

projected to be substantially less and was negative under 

some scenarios in the model. Importantly, irrespective of 

the range of assumptions used, the model projected a net 

public health harm in the short and long terms if the products do not increase net combustible tobacco cessation in 

adults. Warner and Mendez (2019) used a similar approach, 

concluding that potential life-years gained as a result of 

e-cigarette-induced smoking cessation are projected to

exceed potential life-years lost due to e-cigarette-induced

smoking initiation, and that these results held over a wide

range of assessed parameters. In contrast, Soneji and colleagues (2018), using a Monte Carlo stochastic simulation model, found that 2,070 additional current cigarette

smoking adults (25–69  years of age) (95%  CI, -42,900–

46,200) would, because of e-cigarette use in 2014, quit

smoking in 2015 and remain continually abstinent from

smoking for 7  or more years. The model also estimated

168,000  additional never-cigarette smoking adolescents

(12–17 years of age) and young adults (18–29 years of age)

(95% CI, 114,000–229,000) would, because of e-cigarette

use in 2014, initiate cigarette smoking in 2015 and become 

daily cigarette smokers at 35–39 years of age. Based on the

existing scientific evidence related to e-cigarettes and optimistic assumptions about the relative harm of e-cigarette

use compared with cigarette smoking, the authors concluded that e-cigarette use currently represents more

population-level harm than benefit.

In summary, the evidence is inadequate to infer that 

e-cigarettes, in general, increase smoking cessation; factors contributing to the uncertainty include the changing

characteristics of e-cigarettes, the many different contexts

in which they are used, and the limited number of studies

conducted to date. However, the evidence is suggestive
A Report of the Surgeon General

532 Chapter 6

but not sufficient to infer that the use of e-cigarettes containing nicotine is associated with increased smoking cessation compared with the use of e-cigarettes not containing 

nicotine; of important note, the evidence to support this 

conclusion lacks comparison to standard evidence-based 

therapy, and more research on this topic is warranted. 

The evidence is also suggestive but not sufficient to infer 

that more frequent use of e-cigarettes is associated with 

increased smoking cessation compared with less frequent 

use of e-cigarettes; however, future research on this topic 

is also warranted because existing evidence is primarily 

from observational studies that did not control for confounding based on motivation to quit smoking or assess 

potential characteristics of e-cigarette use that may be 

correlated with frequency of use, such as duration of use 

and product nicotine levels. The effects of e-cigarette use 

on smoking cessation will likely be determined by a combination of the physical characteristics of these products; 

how they are used; and how society, policymakers, manufacturers, smokers, and clinicians approach such products. Well-controlled clinical trials and rigorous, largescale observational studies with long-term follow-up will 

be critical to better understand the impact of various 

e-cigarettes under various conditions. E-cigarettes could 

help adult smokers, by reducing the risk of smokingattributable disease, if they completely switch from conventional cigarettes to e-cigarettes and do not partake in 

an extended period of dual use that delays quitting. It is also 

important to consider the extent of health risks posed by 

ingredients that are unique to e-cigarettes but not present 

in conventional cigarettes (Clapp and Jaspers 2017; Gotts 

et al. 2019; Madison et al. 2019). Among those who have 

transitioned completely, the ultimate goal should be to 

also quit the use of e-cigarettes completely in order to 

achieve the maximum individual and public health benefit. However, at the population level, any potential benefits these products confer in terms of increasing cessation 

among adult smokers would need to outweigh potential risks related to use among youth (USDHHS 2014), 

including the already unprecedented increase in the use 

of e-cigarettes among youth that has occurred in recent 

years (Cullen et al. 2018; Miech et al. 2019). It is particularly important to emphasize the current diversity of 

e-cigarette products: they do not comprise a homogenous 

product category, and they have changed rapidly in design 

and characteristics since first entering the U.S. marketplace in 2007. Consequently, much of the existing scientific literature on cessation relates to past generations of 

e-cigarette products. Therefore, further research is needed 

on the effects that e-cigarettes have on smoking cessation, 

including research on:

• Differential effects based on the type of e-cigarette 

product (e.g., newer vs. older devices), 

• Comparison groups (e.g.,  e-cigarettes that do not 

contain nicotine, NRT, no cessation aid), 

• Components in e-cigarette devices and the settings 

at which they are used (e.g.,  temperature of the 

heating coils), 

• Frequency of use (e.g., daily vs. less frequent use), 

• Informational context (e.g., forms of marketing and 

promotion, communication about risk and harm, 

behavioral support for use as a cessation aid), 

• Potential variations in effects across geographies, and 

• Real-world use of e-cigarettes in different regulatory 

contexts.

Such research will shed light on whether and how it 

may be possible to leverage e-cigarettes (or certain types 

of e-cigarette products) to maximize positive smoking cessation outcomes while minimizing adverse consequences 

related to youth initiation and use.

Teachable Moments

with cigarette smoking or when a dentist, periodontist, or 

dental hygienist is treating a smoker). 

Hospitalization

Hospitalization can present an opportunity to 

change behavior, especially if the patient has been hospitalized for a condition caused or exacerbated by tobacco 

Teachable moments—including life changes, disease diagnoses, medical procedures, and screening 

results—can motivate patients to make and sustain a quit 

attempt. Smokers often come into contact with healthcare professionals—including physicians, nurses, medical 

staff, dentists, and pharmacists—during such moments. 

In addition to the specific situations described below, several other situations can also serve as teachable moments 

(e.g., when a pharmacist is dispensing a drug that interacts 
Interventions for Smoking Cessation and Treatments for Nicotine Dependence 533

Smoking Cessation

use. In most cases, hospitalization involves a temporary 

stay in a smokefree (and sometimes tobacco-free) clinical environment, with ready access to smoking cessation 

counseling and pharmacotherapy, at a time when health 

concerns are acutely relevant. Patients who use cessation 

medications for relief of withdrawal symptoms while hospitalized also have the opportunity to familiarize themselves with these medications and their benefits while in a 

clinical setting, potentially leading to a greater likelihood 

that they will subsequently use them to quit smoking 

(Fiore et al. 2012). Research indicates that tobacco cessation interventions delivered in the hospital can reduce 

tobacco use, improve postsurgical outcomes, reduce readmissions, and improve overall patient survival (Cummings 

et al. 1989; Mullen et al. 2015; Mullen et al. 2017; Nolan 

and Warner 2017; Cartmell et al. 2018b). 

Research also indicates that post-hospital follow-up 

is key to achieving and sustaining smoking abstinence, 

as reported in a 2012 Cochrane meta-analysis of 50 randomized or quasi-RCTs evaluating smoking cessation 

interventions initiated in hospital settings (Rigotti et al. 

2012). The meta-analysis found that intensive counseling 

interventions that were initiated in an acute care hospital 

and included at least 1  month of supportive care after 

discharge from the hospital were effective in increasing 

smoking cessation rates postdischarge (RR = 1.37; 95% CI, 

1.27–1.48); adding NRT further increased the treatment 

effect (RR  =  1.54; 95%  CI, 1.34–1.79). No benefit was 

found for less intensive programs, or for adding bupropion. However, a multicenter, double-blind, randomized, 

placebo-controlled trial in which smokers with acute 

coronary syndrome were randomized to receive varenicline initiated in hospital or placebo for 12 weeks, found 

that patients randomized to varenicline had significantly 

higher rates of smoking abstinence and reduction than 

patients randomized to placebo (47.3% 6-month pointprevalence abstinence  vs. 32.5% in the placebo group, 

p <.05) (Eisenberg et al. 2016). All patients in this trial 

also received low-intensity counseling. 

Rigotti and colleagues (2012) found a comparable 

effect for intensive counseling in rehabilitation hospitals after acute care for stroke, coronary heart disease, or 

cancer or chronic disorders, such as diabetes or asthma 

(RR = 1.71; 95% CI, 1.37–2.14). Although not included in 

Rigotti and colleagues (2012), other research has found 

that treatment of tobacco use during a visit to a smokefree 

psychiatric emergency room or during psychiatric hospitalization was associated with reductions in agitation, 

greater abstinence from smoking, and lower readmission 

rates (Allen et al. 2011; Prochaska et al. 2014). For example, 

Allen and colleagues (2011) found that at baseline, participants were at least moderately agitated, and 28% reported 

aggressive behavior during the previous week. The mean 

Agitated Behavior Scale scores for the nicotine replacement group were 33% lower at 4 hours and 23% lower at 

24 hours than the respective scores for the placebo group. 

Trials designed to link hospitalized smokers with 

quitline services have shown mixed results relative to 

standard, brief stop-smoking interventions (Rigotti 

et  al. 2014, 2016; Cummins et  al. 2016; Warner et  al. 

2016). For example, in a 2014 RCT of 397 smokers who 

received a cessation intervention during hospitalization 

at Massachusetts General Hospital, those assigned to the 

treatment condition that included postdischarge followup care were significantly more likely to achieve biochemically validated abstinence 6 months after discharge than 

those assigned to usual care (a referral to the state tobacco 

quitline) (27%  vs. 16%; RR  =  1.70; 95%  CI, 1.15–2.51; 

p = 0.007) (Rigotti et al. 2014). However, in a 2016 RCT, 

patients were randomized to receive brief, in-hospital 

cessation advice or a brief, 5-minute quitline facilitation 

intervention that consisted of either a fax referral or a 

“warm handoff” (direct phone call to enroll the patient and 

arrange for an initial counseling call) to a tobacco quitline. Compared to those who received the brief, 5-minute 

cessation advice, less than 50% of the intervention group 

completed the first quitline intervention call, and results 

suggested no difference in rates of abstinence 6 months 

after discharge (Warner et al. 2016). 

Overall, studies suggest that hospital-based cessation programs can lower readmission rates and are costeffective for hospitals. For example, the Ottawa Model 

for Smoking Cessation—which identifies hospitalized 

smokers and provides in-hospital cessation counseling 

and medications and post-hospitalization follow-up—

demonstrated increased smoking abstinence; lower rates 

of all-cause readmissions, smoking-related readmissions, 

and all-cause emergency department visits; and reduced 

healthcare costs (Mullen et  al. 2017). The continuous 

6-month abstinence rate was 29.4% for the intervention

group versus 18.3% for controls (Reid et  al. 2010). The

largest absolute risk reductions (ARRs) were for all-cause

readmissions at 30 days (13% vs. 7%; ARR = 6% [3–9%];

p  <0.001); 1  year (38%  vs. 27%; ARR  =  12% [7–17%];

p <0.001); and 2 years (45% vs. 34%; ARR = 12% [7–17%];

p <0.001) (Mullen et al. 2017). The greatest reduction in

risk for all-cause visits to the emergency department was

at 30 days (21% vs. 16%; ARR = 5% [0.4–9%]; p = 0.03).

Reduction in mortality was significant by year 1 (11% vs.

5%; ARR = 6% [3% to 9%]; p <0.001) and continued to

be significant at year 2 (15% vs. 8%; ARR = 7% [4–11%];

p <0.001). From the hospital payer’s perspective, delivery

of in-hospital cessation services was cost-effective, with

1-year cost per QALY gained of $C1,386 (Canadian dollars), and lifetime cost per QALY gained of $C68 (Mullen

et al. 2015).
A Report of the Surgeon General

534 Chapter 6

In a study of acute care patients who were current 

smokers and were admitted to and discharged from the 

Medical University of South Carolina between November 

2014 and June 2015, researchers compared unplanned 

readmissions at 30, 90, and 180  days postdischarge 

between (a) current smokers who were exposed to a nicotine dependence treatment service while hospitalized 

with unplanned readmissions and (b)  smokers who did 

not receive the service (Nahhas et al. 2017; Cartmell et al. 

2018b). The treatment service consisted of at least a bedside consult and/or one interactive voice response (IVR) 

follow-up call. At 30 days postdischarge, smokers exposed 

to the nicotine dependence treatment service were about 

half as likely to be smoking as those who did not receive 

the service (51% abstinence vs. 27%) and had significantly 

lower odds of readmission (OR = 0.77, p <.05) than those 

who did not receive the service (Nahhas et al. 2017). Odds 

of readmission remained lower among smokers exposed 

to the intervention at both 90 and 180 days postdischarge 

but were no longer statistically significant (Cartmell et al. 

2018b). In a separate follow-up study, Cartmell and colleagues (2018a) assessed cost savings to the hospital at 

12  months postdischarge, finding that overall adjusted 

mean healthcare charges for smokers exposed to the 

intervention were about $7,300 lower than charges for 

those who did not receive the intervention.

Based on evidence of the effectiveness and benefits of interventions to help hospitalized smokers quit, 

The Joint Commission released an updated set of performance measures on tobacco cessation for hospitals (Fiore et al. 2012) (also see Chapter 7), but the final 

measures no longer contain the postdischarge follow-up 

component. Despite the growing body of evidence that 

hospital-initiated tobacco cessation interventions, especially programs that continue postdischarge, can increase 

abstinence, reduce readmission rates, and lead to cost savings, only about 5% of accredited acute care hospitals in 

the United States have selected and are reporting on the 

tobacco cessation measures from The Joint Commission, 

even without the follow-up component, and the number 

of hospitals reporting on these measures has decreased in 

recent years (The Joint Commission, personal communication, March 18, 2019). This is likely due to the voluntary nature of the measures (they are not currently tied to 

payment)—coupled with the fact that certain other measure sets from The Joint Commission are required or tied 

to payment, with the fact that performance measures are 

increasingly being reported electronically and the Joint 

Commission cessation measures have still not been fully 

converted electronically, and with the perception that 

other measure sets may be easier to implement and report 

on (Freund et al. 2008, 2009). If the cessation measures 

from The Joint Commission are not included in a CMS 

rule or otherwise tied to payment or required, then the 

number of acute care hospitals reporting on these measures is likely to continue to decline. In contrast, two of 

these measures (offering cessation counseling and medication during hospitalization and again at discharge) are 

embedded in the Inpatient Psychiatric Facility Quality 

Reporting Program, and inpatient psychiatric facilities are 

accordingly required to report on these measures.

Surgery

Like being hospitalized, undergoing surgery can be a 

source of motivation to quit smoking, especially if the surgery is related to a health condition caused by smoking and 

presents an opportunity for patients to quit and stay quit. 

Smoking is a risk factor for perioperative and postoperative 

complications (e.g., wound infection, respiratory failure, 

lengthy hospital stays, admission to intensive care unit, inhospital mortality, and readmission) (Lavernia et al. 1999; 

Delgado-Rodriguez et al. 2003; Barrera et al. 2005; Warner 

2006) across a variety of surgical specialties (Brooks-Brunn 

1997; Glassman et al. 2000; Møller et al. 2002; Thomsen 

et al. 2010). Quitting smoking before surgery can improve 

outcomes and reduce healthcare costs (American College 

of Surgeons 2014). Surgery also presents an opportunity 

for patients to quit and stay quit. For example, a large 

cross-sectional study found that having a major surgery 

doubled the likelihood of quitting smoking—particularly 

for surgery related to conditions caused or exacerbated 

by smoking, such as cancer and heart disease (Shi and 

Warner 2010). Even having minor surgery increased quit 

rates by 28%—a finding that, because of the high occurrence of such surgeries, could have a substantial impact 

on population-level tobacco abstinence (Keenan 2009). 

Requiring tobacco cessation and offering cessation treatments before elective surgery could further increase this 

effect. In one study, perioperative patients who were given 

a brief consultation by a nurse, smoking cessation brochures, and access to 6 weeks of NRT and were referred 

to a quitline were 2.7 times more likely to achieve longterm cessation than patients who received usual treatment, which did not include such components (Lee et al. 

2015). Although little research has focused on surgeons 

as providers of tobacco treatment, even brief counseling 

on smoking cessation by a vascular surgeon was found 

to increase patients’ interest in cessation and awareness 

of the harms of smoking, and this effect was maintained 

3 months after the intervention (Newhall et al. 2017). 

The evidence suggests that cessation interventions delivered before and in connection with surgery can 

increase smoking cessation among patients and improve 

surgical outcomes. Based on data from observational 
Interventions for Smoking Cessation and Treatments for Nicotine Dependence 535

Smoking Cessation

studies and systematic reviews of RCTs by Nolan and Warner 

(2017), offering evidence-based tobacco treatments before 

and/or immediately around the time of surgery improves 

surgical, cardiovascular, pulmonary, and wound-healing 

outcomes in the short and long terms. Across more than 

400  studies, effect sizes for improvement of outcomes 

ranged from 1.56 to 2.73 in the treatment group compared 

with placebo, usual care, or brief advice. Thomsen and colleagues (2014) suggested that while the optimal intensity 

and timing of preoperative intervention remain unclear, 

based on indirect comparisons and evidence from two 

small trials, cessation interventions that begin 4–8 weeks 

before surgery, include weekly counseling, and use NRT 

are beneficial to reduce postoperative surgical complications and increase long-term smoking cessation.

Lung Cancer Screening

Lung cancer screening with low-dose computed 

tomography (LDCT) is associated with an estimated 20% 

lower mortality rate from lung cancer relative to chest 

x-ray because of earlier detection of the cancer (Aberle 

et al. 2011; Bach et al. 2012). Based on findings from large, 

well-controlled clinical trials, USPSTF (2015) recommends that LDCT screening be offered to patients at high 

risk for lung cancer, defined as adults 55–80 years of age 

with a 30-pack-year smoking history who currently smoke 

or have quit smoking within the past 15 years. USPSTF 

recommends that screening continue annually until the 

patient has remained abstinent from smoking for 15 years 

or reaches 80 years of age (Moyer 2014). In February 2015, 

CMS issued a national coverage determination requiring 

Medicare to cover LDCT screening for lung cancer if certain eligibility requirements are met, including being 

aged 55–77 years of age, having no signs or symptoms of 

lung cancer, having a tobacco smoking history of at least 

30 pack-years, being a current smoker or one who has quit 

smoking within the past 15 years, and receiving a written 

order for LDCT that meets several criteria (CMS 2015). 

In 2015, an estimated 6.8 million current and former U.S. 

smokers met the criteria for LDCT lung cancer screening 

(Jemal and Fedewa 2017). Medicare reimbursement of 

lung cancer screening requires that smoking cessation 

be addressed (CMS 2015). The shared decision-making 

visit must include counseling on the importance of maintaining cigarette smoking abstinence (if the patient is 

a former smoker) or counseling on the importance of 

smoking cessation (if the patient is a current smoker), and 

providers must offer information about tobacco cessation 

interventions. In addition, eligibility criteria for radiology 

imaging facilities must include making smoking cessation 

interventions available for current smokers.

Because of the criteria for lung cancer screening, 

the population receiving screening by definition includes 

a large number of current longtime smokers. Given the 

heightened awareness of smoking-related cancers among 

patients presenting for LDCT screening, these men and 

women could be especially receptive to smoking cessation advice and interventions delivered throughout the 

screening process (including before, during, and after the 

screening). Research on the perceptions and beliefs about 

smoking and negative health outcomes among high-risk 

older smokers found high levels of awareness of the dangers of continued smoking and strong interest in quitting, even if the screening results showed no signs of lung 

cancer (Cataldo 2016).

Several studies of smokers undergoing a lung 

cancer screening trial found that (a)  motivation to quit 

and quit rates were higher among study participants than 

among those in the general population and (b)  persons 

with abnormal LDCT scans were significantly more likely 

to quit smoking than those without abnormal results 

(Taylor et al. 2007; Styn et al. 2009; Slatore et al. 2014; 

Tammemägi et  al. 2014). For example, in the National 

Lung Screening Trial (a study of 53,454 current or former 

heavy smokers, 55–75  years of age, with 30  or more 

pack-years of smoking), participants with suspicious 

results (a nodule ≥4  mm on the computed tomography 

scan) reported approximately 6% lower rates of smoking 

compared with those with normal results from the scan 

(Slatore et al. 2014; Tammemägi et al. 2014).

Despite these findings, some researchers have posited that, in the absence of a comprehensive cessation 

component, lung cancer screening could potentially have 

a negative impact on smoking cessation, with smokers 

believing that they have already taken sufficient action 

to protect their health simply by undergoing screening 

(Harris 2015; Zeliadt et al. 2015). Such an impact could 

be especially pronounced among smokers who receive 

negative screening results (i.e., no sign of cancer), since 

they might interpret the results to mean that they have a 

clean bill of health and a green light to continue smoking 

(Harris 2015; Zeliadt et al. 2015). In the clinical guideline 

on Pairing Smoking-Cessation Services with Lung Cancer 

Screening issued by the Association for the Treatment of 

Tobacco Use and Dependence and the Society for Research 

on Nicotine and Tobacco, Fucito and colleagues (2016) 

reported that a limited amount of data are available on the 

topic. The small number of studies conducted to date have 

yielded mixed findings.

Several studies seeking to add cessation interventions to LDCT scans have not observed improved cessation outcomes (e.g., Clark et al. 2004; van der Aalst et al. 

2012; Marshall et al. 2016). Most of these trials used minimally intensive cessation interventions (e.g.,  self-help 
A Report of the Surgeon General

536 Chapter 6

materials, lists of resources, tailored computer information), which may have contributed to the lack of significant findings. Some evidence suggests that more intensive cessation interventions delivered in this setting 

might be more effective, and that the timing of such 

interventions may matter. For example, in a pilot study 

in which 18 patients were offered one face-to-face counseling session and follow-up telephone counseling with 

medications, Ferketich and colleagues (2012) found biochemically confirmed quit rates of 33.3% when the cessation intervention was delivered before the lung cancer 

screening (vs. 22.2% when it was delivered later). In addition, Park and colleagues (2015) reported increased quit 

rates when patients undergoing lung cancer screening 

received multisession, more intensive visits that included 

providing assistance (e.g., providing cessation counseling 

and/or prescription medication) and arranging follow-up. 

In summary, although studies of LDCT scans have 

had positive effects on cessation behaviors, the optimal 

smoking cessation strategy for smokers who undergo 

LDCT screening remains unclear (Marshall et  al. 2016), 

and research on the effectiveness of cessation interventions among persons receiving LDCT is still limited 

(Piñeiro et al. 2016). More research is needed to identify 

the most effective types of messaging and other types of 

cessation interventions to increase motivation to quit, 

quit attempts, and successful cessation among smokers 

who undergo lung cancer screening. Eight large RCTs of 

smoking cessation interventions for patients undergoing 

lung cancer screening are underway (Joseph et al. 2018; 

Taylor et al. 2019). These studies, along with future surveillance of populations undergoing lung cancer screening, 

will be critical to better understanding the impact of 

lung cancer screening on smoking and smoking cessation behaviors. In the interim, it is important for clinicians and lung cancer screening sites to deliver cessation 

interventions to this high-risk population and to evaluate 

and report the results to inform best practices in this area.

Readiness to Quit and Approaches 

for Quitting Ambivalence

The Clinical Practice Guideline recommends providing brief motivational counseling to smokers who are 

ambivalent about quitting (Fiore et  al. 2008). Although 

nearly 7 out of 10 adult cigarette smokers reported that 

they want to stop smoking completely (Babb et al. 2017), 

just over 5 out of 10 reported trying to quit in the past year 

(Babb et al. 2017), suggesting that a substantial number 

of smokers are not yet ready to quit or are ambivalent 

about quitting. The Stages of Change Model provides a 

framework for assessing readiness to quit and for tailoring 

interventions accordingly. Cessation strategies tailored 

to a smoker’s readiness to quit are less likely to be perceived as overwhelming because the smoker is less likely 

to feel that these strategies are rushing them into action 

(Hall et al. 2006; Fiore et al. 2008; Prochaska et al. 2014). 

Readiness to quit can be conceptualized as a continuum of 

stages proceeding from precontemplation (no immediate 

intention to stop smoking) to contemplation (intending 

to quit in the next 6 months) to preparation (considering 

quitting in the next month, with at least one quit attempt 

in the past year) to action (has quit smoking for less than 

6 months) and finally to maintenance (has quit smoking 

for at least 6 months) (Prochaska and DiClemente 1983). 

It should be noted, however, that smokers’ progression 

through the stages of change is not necessarily sequential 

or orderly. Rather, smokers’ motivations and readiness to 

quit are transient and fluctuate over time, and smokers 

may make spontaneous, unplanned quit attempts without 

first passing through all the stages of change (West 2005).

Unlike clinically based models, tailoring treatments 

to a smoker’s stage of readiness to change recognizes that 

individual smokers may not always be receptive to certain 

types of cessation interventions. Part of the utility of this 

model is that it identifies a patient’s stage of readiness and 

suggests interventions that can help move the patient to a 

point where he or she is ready to take advantage of standard 

treatment models. Motivational interviewing and adaptations of this approach (reviewed previously in this chapter) 

follow an intervention framework that is distinct from, but 

generally consistent with, stage-based approaches. 

Stage-based, computer-delivered interventions have 

demonstrated efficacy for supporting smokers through the 

process of quitting, including smokers with depression or 

serious mental illness (Prochaska et  al. 1993, 2001a,b, 

2014; Velicer et al. 1999; Hall et al. 2006). In their review 

of 22  stage-based cessation interventions, Riemsma and 

colleagues (2003) found stronger effects in higher quality 

studies and with interventions tailored to all constructs 

of the Transtheoretical Model (Prochaska and DiClemente 

1983), not just to the stage of change (Spencer et al. 2002). 

The review noted generally positive outcomes of the interventions and indicated a clear relationship between study 

quality and statistical significance: only 1 of 5 (20%) lowquality studies, 8  of 14  (57%) moderate-quality studies, 

and 3  of 4  (75%) of the highest quality studies yielded 

a significant finding. However, 1  of the 4  studies in the 

highest quality group had a small sample and a short 

follow-up, and was group-matched on only one stage of 

the Transtheoretical Model. 

Some have argued that applying the Transtheoretical 

Model and Stages of Change Model to smoking cessation 

assigns smokers to stages based on arbitrary time periods 

that are not rooted in the science of smoking cessation 
Interventions for Smoking Cessation and Treatments for Nicotine Dependence 537

Smoking Cessation

(e.g., a smoker ready to quit in 30 days is considered to be 

in the preparation stage, but one ready to quit in 31 days is 

in the contemplation stage [West 2005]). Another potential limitation of a stage-based approach is that it assumes 

that smokers make coherent and stable plans about quitting, but other research suggests that intentions to quit 

may be unstable (Hughes et al. 2005) and that smokers 

may make spontaneous quit attempts with no planning 

or preparation (Larabie 2005; Cooper et al. 2010). Finally, 

because the Stages of Change Model prioritizes intervening with smokers who are preparing to quit or actively 

engaged in quitting, some have argued that this approach 

may fail to offer effective interventions to smokers who 

might have been receptive to them (e.g., smokers who are 

contemplating a quit attempt or who may be ambivalent 

[West 2005]). Indeed, some evidence suggests that cessation assistance should be offered to as broad a spectrum of 

smokers as possible, because current motivation to quit 

does not necessarily predict future abstinence (Pisinger 

et al. 2005). 

Although the Transtheoretical Model and the Stages 

of Change Model have been widely applied to the field of 

smoking cessation and can be used to assess interest in and 

ambivalence about quitting and to tailor cessation interventions accordingly, clinicians should also be advised that the 

manner in which smokers approach quitting at a population level may not map onto these models. Offering support 

to as wide a range of smokers as possible is likely the best 

approach to increase quit attempts and successful quitting. 

However, more research is needed on such an approach, 

including unintended consequences. For example, offering 

widespread support could reduce cost-effectiveness, as 

interventions could be given to more numbers of smokers 

who are not ready and, as a result, would not quit.

Considerations for Subpopulations

As the prevalence of cigarette smoking in the general 

U.S. population has declined over time, increased attention has been devoted to tobacco cessation interventions 

focused on certain subgroups that may be more likely 

to smoke, be heavier smokers, bear a disproportionate 

burden of smoking-related morbidity and mortality, and 

face special challenges in quitting. In some cases, certain 

populations or conditions may warrant specific cessation 

interventions and/or lack an indication for or have certain considerations or contraindications related to cessation medication. This section outlines the evidence and 

considerations for cessation interventions across specific 

populations and/or conditions for which existing interventions are not indicated and/or are less effective. 

Pregnant Women

Pregnant women are a priority population for 

tobacco cessation because of the health risks that tobacco 

use during pregnancy poses to the mother and the fetus 

(USDHHS 2001, 2004, 2014). Furthermore, pregnancy 

can offer an opportunity to quit smoking because pregnant 

women are highly motivated to take actions to protect the 

health of their babies (DiClemente et al. 2000). The literature indicates that, among American women who smoked 

during the 3 months before they became pregnant, about 

50% quit during pregnancy (Tong et al. 2013; Curtin and 

Mathews 2016). However, rates of postpartum relapse 

among women who quit smoking during pregnancy may 

be as high as 50% (Tong et al. 2013). Large variations in 

rates of smoking during pregnancy are seen across subpopulations and states (Curtin and Mathews 2016; Drake 

et  al. 2018). Rates of smoking during pregnancy are 

higher among younger women, women with lower levels 

of education, economically disadvantaged women, and 

women who have not planned their pregnancy (Mosher 

et al. 2012; Curtin and Mathews 2016; Drake et al. 2018). 

Pregnant women and women of reproductive age who 

smoke are also more likely to live in low-resource environments that potentially subject them to high levels of 

stress (Coleman-Cowger et al. 2016; Mazurek and England 

2016), and being pregnant may represent an additional 

stressor for these women. This context provides important insights into the potential challenges of providing 

smoking cessation treatment during pregnancy. 

The Clinical Practice Guideline concluded that 

there was insufficient evidence for the effectiveness of 

smoking cessation medications in pregnant women (Fiore 

et al. 2008). Similarly, USPSTF (2015) concluded that evidence is not sufficient to assess the balance of benefits and 

harms of pharmacotherapy interventions for tobacco cessation in pregnant women. More research is needed before 

definitive guidance can be provided on this topic (Fiore 

et al. 2008; Coleman et al. 2012a, 2015; Myung et al. 2012). 

Results have been mixed in reviews of the use of cessation 

pharmacotherapies (with most of the studies focusing on 

NRT) in women who smoke during pregnancy. These findings suggest that adding NRT to behavioral interventions 

may not increase quitting in this population (Coleman 

et al. 2012a, 2015; Myung et al. 2012). This may be due 

in part to a low medication adherence rate in trials to 
A Report of the Surgeon General

538 Chapter 6

date (Wisborg et  al. 2000; Pollak et  al. 2007; Coleman 

et al. 2012b). 

Pregnant smokers should be encouraged to attempt 

cessation using educational and behavioral interventions 

before using pharmacologic approaches. In individual 

cases, however, women and their physicians may opt to 

use cessation medications, including such alternatives to 

NRT as bupropion or varenicline. However, these decisions should be made in consultation with a physician 

after carefully considering the specific circumstances and 

weighing the risks of using medication against the risks of 

continued smoking (Fiore et al. 2008).

With regard to behavioral cessation interventions 

for pregnant women, USPSTF (2015) recommends that, as 

a Grade A intervention, clinicians ask all pregnant women 

about tobacco use, advise pregnant women who use tobacco 

to stop, and provide behavioral cessation interventions to 

pregnant women who use tobacco. Recent studies have 

suggested that social support is highly predictive of successful smoking cessation during pregnancy (Smedberg 

et al. 2014; Boucher and Konkle 2016). In addition, intervention approaches that address the health of the mother 

and the health of the fetus may increase long-term abstinence (Flemming et al. 2015; Bauld et al. 2017). Cessation 

interventions that are more intensive, are tailored, and go 

beyond advice to quit are more effective in this population (Fiore et al. 2008; Lumley et al. 2009). WHO (2013) 

recommends behavioral cessation interventions—such as 

health education, counseling, social support, and incentives for abstinence—as effective approaches to increasing 

cessation during pregnancy and to improving health outcomes for both the baby and the mother. Quitline counseling may be a useful cessation intervention for pregnant smokers, but more research is needed on the specific 

features that make this intervention optimally effective 

(e.g., the timing and frequency of calls during pregnancy 

and/or postpartum for relapse prevention and tailoring 

approaches) (Bombard et al. 2013; Cummins et al. 2016). 

A growing body of evidence suggests that incentives 

and contingency management techniques (reviewed in 

detail elsewhere in this chapter) are effective cessation interventions for pregnant women (Higgins et al. 2004, 2010b, 

2014; Heil et al. 2008; Cahill et al. 2015). For example, Cahill 

and colleagues (2015) found that incentive-based smoking 

cessation programs produced better outcomes for pregnant women than among controls (OR = 3.6; 95% CI, 2.39–

5.43), with assessments out to 3 months postpartum. The 

same review concluded that such programs improve abstinence while the incentives remain in place. Despite these 

promising results, more evidence is needed to fully understand the effectiveness of incentive interventions in producing sustained cessation outcomes in pregnant women 

who smoke. Although it may be challenging to convince 

payers to implement incentive interventions on a population scale, they may be more willing to consider doing so in 

this case, given the high costs of smoking-related adverse 

birth outcomes and the short-term cost savings associated 

with preventing these outcomes. 

Lesbian, Gay, Bisexual, and 

Transgender Populations

In part because the tobacco industry has directly targeted the lesbian, gay, bisexual, and transgender (LGBT) 

population with marketing and outreach (Washington 

2002; Stevens et al. 2004; Dilley et al. 2008), the prevalence 

of cigarette smoking and other tobacco use is substantially 

higher in these groups than in non-LGBT populations (Hu 

et al. 2016). For example, in a large national health survey 

(Jamal et al. 2016), the prevalence of smoking was higher 

among adults who were lesbian, gay, or bisexual (20.6%) 

than among heterosexual adults (14.9%). In 2015, gay, lesbian, and bisexual adult smokers, as a group, reported a 

lower prevalence of cessation counseling and/or medication 

use (14.5%) when trying to quit than did straight smokers 

(31.7%) (Babb et al. 2017). In addition, transgender adults 

report higher use of cigarettes and other tobacco products than cisgender persons (people whose gender identity matches the sex they were assigned at birth). Data 

from a 2013 nationally representative survey found that 

35.5% of transgender adults reported past-month cigarette 

use compared with 20.7% of cisgender adults (Buchting 

et al. 2017). Although data are not available on the use of 

tobacco cessation treatments by transgender adults, as a 

group they are more likely to postpone general medical 

care and to report barriers in accessing care, primarily 

because they encounter discrimination when seeking care 

and cannot afford care (Grant et al. 2010). 

Reviews of cessation treatments in LGBT populations 

have found that such treatments can be effective, but data 

are limited (Lee et al. 2014; Berger and Mooney-Somers 

2016). In addition to the inclusion of elements of standard 

behavioral cessation treatment, most studies of this topic 

have investigated the effect of cessation interventions 

that have been modified to address LGBT-specific issues, 

including providing information about the tobacco industry’s targeting of LGBT communities, the role of tobacco 

use in LGBT social activities, LGBT-specific smoking triggers, and social justice considerations (Berger and MooneySomers 2016). Notably, a systematic review of 19 LGBTfocused cessation interventions reported cessation rates of 

30–40% out to 3–6 months (Berger and Mooney-Somers 

2016). Although these results appear promising, none of 

the studies used adequate control groups, so a rigorous 

evaluation of efficacy was not possible.
Interventions for Smoking Cessation and Treatments for Nicotine Dependence 539

Smoking Cessation

To more actively engage LGBT communities in 

smoking prevention and cessation, some national smoking 

cessation campaigns (e.g.,  Tips From Former Smokers

[CDC]) have included multimedia promotional materials designed specifically for LGBT populations. In May 

2016, FDA launched This Free Life, a tobacco public education campaign that aims to prevent the escalation to 

daily tobacco use among lesbian, gay, bisexual, and transgender (LGBT) young adults, 18- to 24 years of age, who 

are nondaily or occasional smokers (FDA 2019b). This 

Free Life uses a range of primarily digital marketing tactics, including social media and online advertisements, to 

deliver messages to diverse subpopulations of the LGBT 

community. Evaluations of the effect of these large-scale 

promotions are ongoing, but the data are not yet available. 

Populations with Mental Health 

Conditions and Co-Occurring 

Substance Use Disorders

Mental health conditions and substance use disorders commonly co-occur with smoking. Adults with 

mental health or substance use disorders account for 40% 

of all cigarettes smoked (Substance Abuse and Mental 

Health Services Administration 2013). In 2012–2014, the 

prevalence of cigarette smoking was higher among adults 

with any mental illness than among adults with no mental 

illness (33.3% vs. 20.7%, respectively, p <.05) (Lipari and 

Van Horn 2017). Nationally representative data from 2017 

suggest that tobacco is used by 40.8% of individuals with 

serious psychological distress and 18.5 % of those without 

serious psychological distress (Wang et al. 2018). In 2013, 

65.2% of adult cigarette smokers also reported using 

alcohol (vs.  48.7% of nonsmoking adults), and 18.9% 

reported past-month use of other drugs (vs. 4.2% of nonsmoking adults) (Substance Abuse and Mental Health 

Services Administration n.d.). Behavioral health conditions also affect smoking patterns in ways that can make 

quitting more difficult. For example, the average number 

of cigarettes smoked in the past month was higher among 

adult smokers with any mental illness (326) than among 

adult smokers with no mental illness (284) (Lipari and 

Van Horn 2017). 

The high prevalence of smoking among persons with 

mental illness is due in part to their lower rates of quitting smoking over time (Prochaska et al. 2017). In addition, mental illness is associated with heavier smoking, 

greater nicotine dependence, more pronounced withdrawal symptoms when quitting, and lower quit rates (Hall 

and Prochaska 2009). Although research on smoking and 

mental illness has increased markedly in recent years, 

cessation intervention studies on this population are still 

limited. A statistical analysis of the literature on tobacco and 

mental illness documented a steady increase in research 

publications in this area for three 2-year periods: 1993–1995 

(n = 65), 2003–2005 (n = 153), and 2013–2015 (n = 329) 

(Metse et al. 2017). However, the study designs remained 

predominantly descriptive in form (>80%), and few experimental studies tested cessation interventions (<13%).

A meta-analysis of 26 tobacco intervention studies 

found that smoking cessation was significantly associated 

with decreases in anxiety, depression, and stress and with 

improvements in overall mood and quality of life (Taylor 

et al. 2014). Notably, the strength of these relationships did 

not vary based on the presence or absence of a psychiatric 

diagnosis. In trials of tobacco cessation interventions conducted among smokers with psychiatric disorders, quitting 

smoking was associated with reductions in depression, anxiety, and symptoms of posttraumatic stress disorder and 

psychosis and with rapid changes in mood (Potkin et al. 

2003; McFall et al. 2010; Kahler et al. 2011; Krebs et al. 

2016). A meta-analysis that focused on smokers in treatment for substance use disorders found that tobacco cessation interventions were associated with a 25% increased 

likelihood of abstinence from alcohol and other drugs relative to usual care (Prochaska et al. 2004). A randomized 

trial of smokers recruited from inpatient psychiatric facilities found that a tobacco cessation intervention was associated with a significantly lower likelihood of readmission 

(Prochaska et al. 2004). In the past, many behavioral health 

clinicians believed that treating nicotine dependence and 

tobacco cessation jeopardize sobriety or mental health 

recovery (Baca and Yahne 2009), a misconception that has 

been actively fostered by the tobacco industry (Prochaska 

et al. 2008; Hall and Prochaska 2009). However, smoking 

cessation and the delivery of tobacco cessation treatments 

are associated with enhanced clinical outcomes, including 

improved sobriety, fewer symptoms of posttraumatic stress 

disorder, and lower rates of hospitalization.

Another RCT was conducted in 10 community 

mental health centers to determine whether smokers 

with schizophrenia or bipolar disease have higher rates of 

tobacco abstinence with pharmocotherapy than with standard treatment (Evins et al. 2014). There were 87 smokers 

with schizophrenia or bipolar disease who received 

12 weeks of varenicline and achieved 2 weeks or more of 

continuous abstinence by week  12 who were randomly 

assigned to receive cognitive behavioral therapy and varenicline or placebo. At week 52, biochemically verified 7-day 

point-prevalence abstinence rates were 60% in the varenicline group (24 of 40) versus 19% (9 of 47) in the placebo 

group (OR = 6.2; 95% CI, 2.2–19.2; P < .001). The authors 

concluded that among smokers with serious mental illness 

who attained initial abstinence with standard treatment, 
A Report of the Surgeon General

540 Chapter 6

maintenance pharmacotherapy with varenicline and cognitive behavioral therapy improved prolonged tobacco 

abstinence rates compared with cognitive behavioral 

therapy alone after 1 year of treatment and at 6 months 

after treatment discontinuation (Evins et al. 2014).

Approaches to smoking cessation with demonstrated 

efficacy among smokers with mental illness or addictive 

disorders include motivational and stage-based treatments and behavioral therapy that is offered outside of or 

integrated within mental health or addictions treatment, 

delivered in person or via a quitline, and combined with 

cessation pharmacotherapy (Hall and Prochaska 2009). 

The California Smokers’ Helpline reported that nearly 

1  in 4  of 844  smokers who called the helpline in 2007 

and were screened for depression, met criteria for a current major depressive disorder and that quit rates at the 

2-month follow-up were lower in this group (19%) than 

among callers without depression (28%) (Hebert et  al. 

2011). More generally, the convenience and accessibility 

of quitlines make them an important option for clinician 

referrals among this population. Supplementary cessation 

services and treatments that can complement clinician 

and quitline interventions, such as in-person counseling 

and cessation medication, may further increase quit rates. 

A randomized trial of 577 mental health patients in the 

Veterans Health Administration found that a specialized 

quitline for smokers referred by a mental health provider 

outperformed standard state quitlines, with significantly 

greater 30-day abstinence at 6 months (26% vs. 18%) and 

greater patient satisfaction (Rogers et al. 2016).

A Cochrane Review of trials testing smoking cessation interventions that included specific mood management components for depression versus a standard intervention showed a significant positive effect for smokers 

with current depression (11 trials; N = 1,844; RR = 1.47; 

95% CI, 1.13–1.92) or past depression (13 trials; N = 1,496; 

RR = 1.41; 95% CI, 1.13–1.77) (van der Meer et al. 2013). 

The interventions largely followed a behavioral therapy 

approach, offering group or individual counseling sessions. For example, the treatments encouraged participants to monitor their mood with a daily rating scale and 

to learn and apply skills to decrease negative moods and 

increase pleasant ones—such as by recognizing maladaptive thoughts, disputing negative thinking, engaging in 

pleasant activities, increasing positive social contacts, and 

setting realistic goals (Hall et al. 1994, 1996). 

Researchers have also tested the use of medications 

for mood management when quitting smoking. In  one 

systematic review, use of bupropion and nortriptyline, 

which are both antidepressants, resulted in a statistically 

significant increase in tobacco abstinence, irrespective of 

depression history, but selective serotonin reuptake inhibitors (e.g., fluoxetine, sertraline) and monoamine oxidase 

inhibitors (MAOIs) were not found to increase smoking 

cessation (Hughes et al. 2014). 

Postmarketing reports, which are mandated by 

FDA, have raised concerns that persons taking varenicline 

may experience increased intoxicating effects when consuming alcoholic beverages. However, these effects have 

not been observed in clinical trials. Instead, evidence suggests that varenicline may aid in quitting smoking while 

also reducing drinking in men who drink excessively. 

A  double-blind RCT of 131  smokers (30% women) with 

alcohol use disorders found that varenicline with medical 

management resulted in an increased rate of smoking 

abstinence overall and in decreased heavy drinking among 

men (O’Malley et al. 2018). These findings are important 

in light of the high rate of comorbid smoking and heavy 

drinking, but more research is needed. 

In conclusion, individuals with behavioral health 

conditions smoke at a significantly higher rate than the 

general population and generally have a more difficult 

time quitting, despite being equally interested in quitting. 

However, evidence increasingly suggests that quitting 

smoking does not jeopardize the success of treatment for 

mental health conditions or substance abuse and may actually enhance recovery outcomes (McKelvey et  al. 2017). 

Additional research is needed on which tailored tobacco 

cessation interventions are most effective in helping persons with behavioral health conditions quit smoking. 

Adolescents

Nearly 9  out of 10  smokers first try smoking by 

18 years of age, with 99% of smokers doing so by age 26 

(USDHHS 2012, 2014). Accordingly, tobacco use can be 

considered a pediatric disorder (USDHHS 2012). Other 

data suggest that initiating tobacco use at 13 years of age 

or younger is associated with continuous daily and nondaily use during adolescence and with the development 

of nicotine dependence, compared with initiating tobacco 

use at 14 years of age and older (Sharapova et al. 2018). 

Once adolescents progress to established smoking, few of 

them attempt to quit, few quit successfully when trying on 

their own (7%), very few seek help quitting, and success 

rates are low—even among those who obtain help (12%) 

(Sussman et al. 1999; USPSTF 2016). Estimates suggest 

that quitting smoking before 35 years of age prevents much 

of the harm from smoking (Doll et al. 2004; Jha et al. 2013; 

Pirie et al. 2013). However, the average age of quitting in 

the United States is approximately 40  years of age, and 

this age did not change significantly between 1997–98 and 

2011–12 (Schauer et  al. 2015a). Because most smokers 

start young and because quitting is difficult once smoking 

becomes established, efforts to prevent adolescents from 
Interventions for Smoking Cessation and Treatments for Nicotine Dependence 541

Smoking Cessation

ever starting to smoke and to help adolescents who start 

smoking to quit as soon as possible are critical. 

The evidence for the effectiveness of cessation interventions targeting youth is mixed. A 2013 systematic review 

by USPSTF found stronger evidence for interventions by 

primary care providers to prevent youth smoking initiation than for provider actions to help youth who already 

smoke quit. The review concluded that, while primary 

care-based behavioral interventions may prevent smoking 

initiation among youth, these interventions, alone or in 

combination with cessation medications (bupropion or 

bupropion plus NRT), have not been shown to increase 

rates of smoking cessation among youth (Patnode et  al. 

2013). The review included studies of smokeless tobacco 

cessation interventions and very brief advice, as well as 

limited print-based interventions. In a Cochrane Review 

of primary care- and school-based tobacco cessation interventions for young people, which had broader criteria for 

including trials, included smokers younger than 20 years 

of age, and pooled data from 28 controlled trials, Stanton 

and Grimshaw (2013) identified as “promising” those 

approaches that were based on the Stages of Change Model 

(pooled RR = 1.56 at 1 year; 95% CI, 1.21–2.01) or included 

motivational enhancement therapy (RR  =  1.60; 95%  CI, 

1.28–2.01). Only 3 of the 28 trials tested pharmacologic 

approaches, and those trials reported limited efficacy. 

Cessation medications are not approved by FDA 

for use with children or adolescents, and NRT cannot 

be purchased over-the-counter by persons younger than 

18 years of age (Johnson et al. 2004; Karpinski et al. 2010). 

However, cessation medications can be prescribed for and 

used by youth under the supervision of a physician. The 

Clinical Practice Guideline found insufficient evidence for 

the effectiveness of cessation medications in adolescents 

(Fiore et al. 2008). A study of 120 smokers 13–17 years of 

age found that the nicotine patch, but not nicotine gum, 

had a statistically significant effect on prolonging abstinence relative to placebo (Moolchan et  al. 2005). More 

explicit evidence-based recommendations are needed to 

guide clinicians and parents in weighing the potential 

benefits and risks of specific smoking cessation medications in adolescent patients (Federal Register 2018).

With regard to behavioral smoking cessation interventions for children and adolescents, a 2016 metaanalysis of such interventions in primary care settings 

found a 34% increase in quit rates relative to control conditions (RR = 1.34; 95% CI, 1.05–1.69), with an absolute 

effect of 7.98% for cessation and a number needed to treat 

of 13  (95%  CI, 6–77) (Peirson et  al. 2016). The review 

excluded studies of smokeless tobacco, brief counseling, 

print materials, and NRT. Of the four studies reviewed, the 

intervention with the strongest effect (a 24% reduction in 

smoking) was based on the Stages of Change Model and 

was personalized, computer assisted, and motivationally 

tailored (Hollis et al. 2005). Adolescents were recruited in 

a clinic setting, and the intervention lasted 12 months. The 

intervention focused solely on tobacco use (rather than 

addressing tobacco use in conjunction with additional risk 

behaviors) and included educational components (Hollis 

et  al. 2005). Further research is needed to identify and 

replicate best practices for tobacco cessation interventions with adolescent smokers. However, recruitment is 

a major challenge to research on cessation among youth, 

in part because of parental consent and youth emancipation laws that are in place in most states. At this juncture, 

focusing on prevention efforts in youth (USDHHS 2012) is 

likely to yield the greatest impact in terms of reducing the 

prevalence of tobacco use in future generations. However, 

continued efforts are warranted to develop effective cessation treatments and interventions for young people who 

are already established cigarette smokers or established 

users of e-cigarettes or other tobacco products and who 

may already be addicted to nicotine. 

Dual Tobacco Product Users

Dual tobacco use, which is commonly defined as the 

use of cigarettes concurrently with other tobacco products (including e-cigarettes), has become increasingly 

common. Among current adult e-cigarette users in the 

2017 National Health Interview (NHIS) Survey, 49.6% 

were current smokers of conventional cigarettes (NHIS 

public use data 2017). Per data from NHIS, nearly 60% 

of adult e-cigarette users in 2015 were also current cigarette smokers, suggesting that dual use of e-cigarettes 

and cigarettes is a common pattern (CDC 2016). In fact, 

this was the most common product combination among 

adults who reported using two or more tobacco products. A study using data from the PATH Study found that 

more than one-third (37.8%) of adult tobacco users in 

2013–2014 were multiple-product (or polytobacco) users, 

with the most common combination being cigarettes 

plus e-cigarettes (Kasza et al. 2017). Among the sample 

of youth (12–17 years of age) in the PATH Study, 43% of 

those using tobacco in the previous 30 days were multipleproduct users; again, cigarettes plus e-cigarettes was the 

most common combination, followed by cigarettes plus 

cigarillos. In the 2018 National Youth Tobacco Survey, 

the prevalence of multiple product use among current 

tobacco users of high school age was 37% for girls and 

45% for boys (Gentzke et  al. 2019). A  probability-based 

survey of 1,836  cigarette smokers found that concurrent use of cigarettes and alternative tobacco products 

(loose leaf chewing tobacco, moist snuff, snus, dissolvable tobacco, or e-cigarettes) was positively associated 
A Report of the Surgeon General

542 Chapter 6

with making cessation attempts and having intentions to 

quit but was not associated with quit success (Popova and 

Ling 2013). A larger study of quit attempts and interest in 

quitting among 26,000 smokers found no clear differences 

between cigarette-only use versus dual use of cigarettes 

and cigars or smokeless tobacco (Schauer et al. 2016b).

A few studies have compared quitting behaviors 

between adult cigarette-only users and dual users. In the 

2010–2011 Tobacco Use Supplement to the Current 

Population Survey, cigarette-only and dual users (defined 

as users of cigarettes plus cigars or smokeless tobacco) 

reported a comparable prevalence of attempts to quit 

cigarettes, with both groups making suboptimal use 

of evidence-based cessation treatments (Schauer et al. 

2016b). Other studies have suggested that many cigarette 

smokers who are trying to quit are using e-cigarettes as 

one method of quitting, as discussed previously in this 

chapter (Caraballo et al. 2017; Zhu et al. 2017). An online 

survey of 1,324 adults found that dual use of cigarettes 

with smokeless tobacco was associated with past attempts 

to quit smoking by switching to smokeless products, while 

dual use of cigarettes with e-cigarettes was associated with 

prior use of cessation medications and strong sentiment 

against the tobacco industry (Kalkhoran et al. 2015). 

Although at least one-third of tobacco users are dual 

users, most trials of tobacco treatments focus exclusively 

on cigarette smoking cessation and do not address cessation interventions for other types of tobacco products. 

While noting that all tobacco products deliver toxicants 

and pose health risks, the 2014 Surgeon General’s report 

concluded that the overwhelming burden of death and disease from tobacco use in the United States is caused by cigarettes and other combustible tobacco products (USDHHS 

2014). The report also acknowledged that the recent shift 

in patterns of tobacco use could have several potential 

impacts, ranging from the positive effect of accelerating 

the rate at which smokers completely quit smoking cigarettes to the negative effect of delaying complete cessation 

of all tobacco products, especially cigarettes. Despite the 

general acceptance of a continuum of risk across tobacco 

products (USDHHS 2014), the specific risk posed by each 

class of tobacco products has not been established and is 

difficult to estimate with precision because of the wide 

spectrum of products within each product class and the 

differences in how they are used. 

Although the use of noncombustible tobacco products does not expose users to the same mix of toxicants 

via the same mode of administration as cigarette smoking, 

all tobacco products carry inherent risks. Risks for dual 

users may be particularly harmful if they delay cessation 

from combustible tobacco (USDHHS 2014, 2016). For 

example, smokeless tobacco has been shown to cause cancers of the mouth, esophagus, and pancreas; diseases of 

the mouth; and adverse reproductive outcomes (WHO 

and International Agency for Research on Cancer 2007; 

USDHHS 2014; NCI and CDC 2014). E-cigarettes emit 

fewer and lower levels of certain harmful substances than 

conventional cigarettes, but the long-term health risks 

of using these products remain unknown, and shortterm risks are only slowly coming into focus. Several 

studies demonstrate e-cigarette aerosol contains fine and 

ultrafine particles, such that use of the products could 

potentially increase cardiovascular and respiratory risks 

(USDHHS 2016; Alzahrani et al. 2018; Nabavizadeh et al. 

2018; National Academies of Sciences, Engineering, and 

Medicine 2018; Gotts et  al. 2019). Therefore, only complete cessation of all tobacco products fully eliminates all 

tobacco-related health risks. Nevertheless, based on currently available evidence, nonpregnant adults would be 

expected to reduce their risk of smoking-attributable disease and death if they completely substituted all combustible tobacco products with noncombustible tobacco products. Whether these products will realize the potential of 

harm reduction depends in part on how their use affects 

smokers’ attempts to quit cigarettes—either by switching 

completely to a noncombustible tobacco product or by discontinuing all tobacco use—combined with their impact 

on youth uptake of e-cigarettes and other tobacco products.

The Clinical Practice Guideline called for more 

research on effective cessation medications and counseling 

interventions for persons who are dual users of cigarettes 

and smokeless tobacco (Fiore et  al. 2008), but research 

in this area remains sparse more than 10 years after the 

Guideline was released. In one study, an interactive, tailored, web-based intervention for smokeless tobacco use 

was found to significantly increase (nearly double) the likelihood of participants abstaining from all tobacco products 

(Severson et al. 2008). Another study examined the impact 

of a 40-minute, single contact, tobacco cessation intervention among 1,055 airmen enrolled in technical training in 

the U.S. Air Force (USAF) (Little et al. 2016). The USAF 

intervention addressed cigarettes, smokeless tobacco, 

snus, cigars, cigarillos, pipes, e-cigarettes, “roll your own” 

cigarettes, and hookah. From before the training to immediately after the training, perceptions of harm increased 

for all nine tobacco products among both tobacco users 

and nonusers, but intention to consume tobacco products was reduced mainly among existing tobacco users. 

Behavioral outcomes were not assessed, given the short 

assessment window (Little et al. 2016).

Much remains to be learned about best practices 

for achieving and sustaining abstinence from all tobacco 

products among dual users. Although few interventions 

have been studied for cessation from all tobacco products, some cessation medications (bupropion, varenicline, NRT) have been found to be effective for cessation 
Interventions for Smoking Cessation and Treatments for Nicotine Dependence 543

Smoking Cessation

from cigarettes and smokeless products (independently) 

(Ebbert et al. 2007; Fagerström et al. 2010; Cahill et al. 

2016; Schwartz et al. 2016; Hartmann-Boyce et al. 2018). 

Such medications could be candidates for tobacco cessation efforts among dual users of those two products. 

More also needs to be learned about (a)  the degree to 

which e-cigarettes may promote or impede efforts to quit 

smoking and (b)  the relative health benefits or harms 

from cessation of one tobacco product, but not all tobacco 

products, among dual or multiple tobacco product users.

Light and Nondaily Tobacco Users

The prevalence of daily smoking has decreased over 

the past two decades, but the proportion of light cigarette 

smoking (usually defined as 10 or fewer cigarettes smoked 

per day) has generally increased (Pierce et al. 2009; Jamal 

et al. 2018) and the prevalence of nondaily smoking has 

been generally stable (Schauer et al. 2016a). For example, 

among current U.S. smokers, the proportion of daily 

smokers was 76.1% in 2016, which declined from 80.8% 

in 2005 (p trend <0.05) (Jamal et al. 2018). During 2005–

2016, increases occurred in the proportion of daily smokers 

who smoked 1–9 cigarettes per day (16.4% to 25.0%) or 

10–19 (36.0% to 39.0%) cigarettes per day, and decreases 

occurred in the proportion of daily smokers who smoked 

20–29 (34.9% to 28.4%) or ≥30 (12.7% to 7.5%) cigarettes 

per day (p trend <0.05) (Jamal et al. 2018). Nationally representative data from 2015 indicate that 24.3% of all smokers 

were nondaily smokers, and 25.1% of current daily smokers 

were light smokers (defined in this study as smoking 

1–9 cigarettes per day) (Jamal et al. 2016). Nondaily smokers 

often do not consider themselves to be smokers; up to 42% 

classify themselves as nonsmokers when asked (Fergusson 

and Horwood 1995). Consequently, nondaily smoking is 

under-recognized by clinicians (Schane et al. 2009), which 

might result in their being less likely to deliver cessation 

interventions to this group of smokers. Studies have also 

pointed to potential challenges in motivating light and 

nondaily smokers to quit, given they are more likely to 

concurrently use other tobacco products than are heavier 

smokers (Reyes-Guzman et al. 2016). On the other hand, 

some studies have found that nondaily smokers report 

greater intention to quit and are more likely to succeed 

in quitting than daily smokers (Hennrikus et  al. 1996; 

Sargent et al. 1998). Whereas daily smokers’ intentions to 

quit may be driven in part by their level of nicotine dependence, nondaily smokers’ intentions to quit may be more 

related to situational cues and sociodemographic characteristics (Fagan et al. 2007; Shiffman et al. 2014).

Most tobacco cessation interventions target daily 

heavy smokers (Fiore et  al. 2008). However, cessation 

interventions are also critically important for nondaily 

and light smokers, but cessation approaches for these 

populations may require a new treatment paradigm 

(Hassmiller et al. 2003; Wortley et al. 2003). The Clinical 

Practice Guideline concluded that there was insufficient 

evidence for the effectiveness of using cessation medications in persons who smoke fewer than 5–10 cigarettes per 

day (Fiore et al. 2008). A review by Lindson and colleagues 

(2019) identified few studies on the role of NRT for persons smoking fewer than 15 cigarettes per day.

Furthermore, preliminary data suggest that standard cessation counseling that focuses on calling attention to personal health risks may not motivate nondaily 

or light smokers to quit, in part because they may believe 

that they have already minimized their health risks by 

using tobacco less intensively (Hyland et al. 2005; Tong 

et  al. 2006). Despite these beliefs, studies indicate that 

light and nondaily smoking significantly increases risk 

for tobacco-related disease, especially cardiovascular and 

respiratory harms (Luoto et  al. 2000; Hackshaw et  al. 

2018; Kameyama et  al. 2018) and all-cause mortality 

(Inoue-Choi et al. 2017; Løchen et al. 2017). Moreover, the 

dose-response relationship between cigarette consumption and cardiovascular risk is not linear (USDHHS 2010).

Studies testing the impact of messages about the 

health harms associated with cigarette smoking generally have not focused on specific tobacco-related harms 

that are relevant to light and nondaily smoking. Messages 

about these effects could be more impactful for these 

groups of smokers, both clinically and at a population 

level, and should continue to be studied.

Data from observational and pilot studies of treatments suggest that counseling nondaily smokers on the 

dangers that their secondhand smoke poses to others could 

also be an effective approach for motivating them to quit 

(Tong et al. 2006; Schane and Glantz 2008; Schane et al. 

2013). In the 1970s, research conducted by the tobacco 

industry concluded that social, infrequent, or nondaily 

smokers felt immune to the personal health effects of 

tobacco use but were concerned about the effects that 

their secondhand smoke might have on others (Schane 

et al. 2009).

Although further research on cessation interventions for nondaily smokers is needed, emerging evidence 

suggests that educating nondaily smokers about the dangers that secondhand smoke poses to nonsmokers is a powerful cessation message and may be more effective than 

traditional smoking cessation counseling that emphasizes 

the health consequences for the smoker (Schane et  al. 

2013). In addition, improved clinical identification of light 

and nondaily smokers is needed to help clinicians target 

these groups with strong messages emphasizing that no 

level of smoking is safe. 
A Report of the Surgeon General

544 Chapter 6

Emerging Behavioral Treatments

In considering potential future directions for behavioral smoking cessation treatments, a wide variety of possible strategies exist to increase their reach while maintaining or improving their efficacy, thus increasing their 

impact. Two innovative approaches are (1) the expansion 

of treatment targets and (2) the use of emerging technologies to better time and personalize the delivery of behavioral cessation interventions.

Expanding Behavioral Treatment Targets

Although behavioral therapy is well established as 

the mainstay of most empirically based behavioral cessation interventions, applying constructs from other psychological theories could potentially enhance the efficacy 

of these interventions. Two examples are (1)  treatments 

drawn from self-determination theory (SDT) (Ryan and 

Deci 2000; Ng et al. 2012) and (2) comprehensive, intensive group treatment for nicotine dependence (Hajek et al. 

1999; Foulds et al. 2006; Hall and Prochaska 2009; Hall 

et al. 2011; Kotsen et al. 2017). 

SDT postulates that a necessary condition for sustained change in health behavior is satisfaction of the basic 

psychological needs that a person has for autonomy, competence, and relatedness (Williams et  al. 2016). Persons 

will be more motivated to change their behaviors and perceive themselves as more capable of successfully changing 

their behaviors in social contexts that support these needs 

(Ng et al. 2012). SDT-based interventions target adaptive 

and maladaptive behaviors and motivations for behavioral change. SDT-based treatments focus on shifting a 

patient’s motivation for behavior change from the external 

(e.g., because others want the patient to change) to the 

internal (e.g.,  the patient wants to change because it is 

consistent with his or her personal values). SDT involves 

working with clients to better align their motivations and 

behaviors to enhance motivation that supports sustained 

behavioral change (Ryan et al. 2008). SDT-based interventions have demonstrated efficacy in a variety of contexts 

and populations, including among persons attempting 

to achieve long-term changes in health behavior, such as 

quitting smoking, losing weight, and engaging in physical 

activity (Williams et al. 2002, 2006a,b, 2009, 2011, 2016; 

Pesis-Katz et al. 2011; Teixeira et al. 2015). 

Although not a new concept, intensive comprehensive tobacco use treatment at the group level likely brings to 

bear unique cessation mechanisms that have consistently 

led to high quit rates. Such treatment is professionally led 

and addresses key mechanisms of behavior change, such 

as group interactions, intergroup discussions between 

smokers, development of cohesion among group members, and support for interventions that are unique to 

this cessation format (Hajek et  al. 1985, 1989; Yalom 

and Leszcz 2005; Kotsen et  al. 2017). Professionally led, 

group-based treatment has been a standard of care in all 

programs designed to treat other types of addictions, and 

has been shown to yield high rates of satisfaction and positive experiences for smokers (Dobbie et al. 2015). For more 

than two decades, these group smoking cessation interventions have shown robust feasibility, acceptability, and efficacy in a range of research and practice settings (Connett 

et  al. 1993; Foulds et  al. 2006; Hall et  al. 2009; Dobbie 

et  al. 2015; Kotsen et  al. 2017; Public Health England 

September 2017), to the point that they can be applied in 

all healthcare settings (including primary and specialty 

care) and behavioral healthcare settings. However, group 

interventions have traditionally been limited by their 

reach, because having to travel to an in-person meeting 

at a set meeting time can be a barrier for many smokers, 

particularly those with lower incomes. Future research 

could explore whether combining medication with intensive group smoking cessation treatment led by a tobacco 

treatment specialist is feasible in a virtual telemedicine, 

telehealth, or other technology-based format, which could 

broaden the reach and availability of this approach.

Use of Emerging Technology

Given the dynamic, quickly evolving nature of the 

personal technology modalities used in mHealth, it is 

challenging to predict future developments in this area. 

More sophisticated applications are being developed 

that involve context-dependent, adaptive interventions 

and that are tailored to the needs of each individual. For 

example, just-in-time interventions are designed to prevent relapse when a smoker is at greatest risk, including 

using sensors (e.g., through GPS monitoring) that track 

a person’s location and trigger support when the person 

enters a high-risk environment (e.g., when the person 

approaches a tobacco retailer) (Naughton 2016). Such 

innovations may lead to interventions that improve cessation outcomes in ways that could not have been achieved 

without such technology. Furthermore, the commercialization of smoking cessation interventions delivered by a 

variety of mobile applications may lead to some promising 

approaches. However, the proliferation of these applications has far surpassed the capacity for the scientific evaluation of their content and effectiveness—thus, raising 

Emerging Intervention Approaches
Interventions for Smoking Cessation and Treatments for Nicotine Dependence 545

Smoking Cessation

concerns about their effectiveness and about how these 

interventions adhere to evidence-based recommendations 

for cessation (Abroms et al. 2013).

Ongoing smoking cessation research is exploring 

the utility of two specific approaches that do not rely 

on a particular technology platform. The first approach 

involves improving both the personalization of mHealth 

platforms and engagement with these platforms via 

the use of human-technology interactions that mimic 

human–human interactions. Basic versions, which are 

already widely used in commercial settings for other purposes, include voice phone trees and web pop-ups that 

are designed to help triage the caller or website user to 

the appropriate customer service representative or salesperson. More complex versions help consumers make decisions about which product to buy in a manner that structures the interaction as a conversation (commonly called 

“chatbots”). Future mHealth cessation interventions may 

leverage these structured human-technology interactions 

to deliver highly personalized, real-time cessation support. 

A second strategy involves integrating treatment 

data from multiple sources so that the person delivering 

the cessation intervention and the smoker have access 

to a broader array of information and treatment options 

across multiple contexts. One example is integrating data 

from a quitline’s database with a cessation application on 

a caller’s smartphone. Although many cessation treatment 

approaches, such as quitlines, employ mHealth resources, 

integration across multiple platforms is rare. As with integration across treatment resources, the wide availability 

of electronic health records has created the possibility 

for increased connectivity between healthcare providers 

engaged in cessation treatment (see Chapter 7).

A large number (>500) of smartphone apps for quitting smoking have been developed, and these apps have 

generated great interest (>20 million downloads globally) (Bricker et al. 2014b). These apps include interactive 

features, present content in various formats, and collect 

information that the smartphone then exchanges with 

external databases. Apps have many characteristics that 

can be leveraged to deliver behavioral treatment and to 

improve adherence to medication. Although reviews have 

identified some high-quality cessation apps, many cessation apps lack appropriate, empirically based clinical 

approaches that are consistent with cessation guidelines 

(Abroms et al. 2011, 2013; Choi et al. 2014; Hoeppner et al. 

2016; Ubhi et al. 2016). As with SMS text programs, there 

is wide variability in content, functionality, and user experience across even those apps that use empirically based 

cessation treatment approaches, which makes evaluating 

their utility difficult.

Social media sites are visited by 80% of U.S. adults 

who have access to the Internet, and most of these adults 

visit such sites daily (Greenwood et al. 2016). Research into 

the potential utility of social media platforms for delivering and supporting cessation treatment is in its early 

stages. One logical and promising strategy is to leverage 

social media’s potential for facilitating self-help groups. 

This potential has not been fully realized to date because, 

as with such previous technologies as online bulletin 

boards and listservs, prolonged engagement is often poor, 

with initially high levels of interest often waning over time 

(Danaher et al. 2006; An et al. 2008; Stoddard et al. 2008; 

Prochaska et al. 2012). In one example of an emerging cessation intervention, Twitter is being used to create small, 

private groups of 20 smokers who interact for 100 days, 

with twice-daily automessages sent to encourage group 

engagement among members (Lakon et  al. 2016). The 

intervention builds on successful past work with “buddy 

interventions” in which smokers were assigned physically 

proximal “buddies” who were also trying to quit (West et al. 

1998; May and West 2000; May et al. 2006). Preliminary 

results for the Twitter intervention indicate that participants in quit-smoking groups often form mutually reciprocated, strong, and enduring social bonds that support 

smoking cessation (Lakon et al. 2016).

In another intervention, which was assessed in an RCT 

pilot, all 160 participants were linked to Smokefree.gov and 

provided with nicotine patches. A subgroup of these participants was randomized to participate in a quit-smoking 

group on Twitter; the study found that they were twice as 

likely to report sustained abstinence as those who used the 

website and patch alone (40% vs. 20%, OR = 2.67; 95% CI, 

1.19–5.99) (Pechmann et  al. 2017). Similar efforts are 

underway to leverage Facebook and WhatsApp to engage 

young adults in cessation treatment. Cessation interventions leveraging these social media platforms have shown 

encouraging short-term effects (Cobb et al. 2014; Cheung 

et  al. 2015; Haines-Saah et  al. 2015; Ramo et  al. 2015; 

Baskerville et al. 2016).

Emerging Pharmacologic 

Approaches

Cytisine, which is not currently approved for use 

in the United States, was first used for quitting smoking 

more than 50 years ago in Eastern and Central Europe, 

well before the approval of any smoking cessation aids in 

the United States. A plant alkaloid with high affinity for 

the α4β2 nicotinic acetylcholine receptor subtype, cytisine 

is derived from the plant Cytisus laburnum. The course of 

treatment starts at one tablet every 2  hours (maximum 

of six tablets total per day) for days  1–3, with a scheduled quit date at day 5, tapered to one or two tablets daily 

by days 21–25 (Jeong et al. 2015). In meta-analyses, the 
A Report of the Surgeon General

546 Chapter 6

treatment effect of cytisine was comparable to published 

effects for NRT, bupropion, nortriptyline, and clonidine 

(Hajek et al. 2013a). Two randomized placebo-controlled 

trials also found that cytisine was effective for smoking 

cessation (pooled effect: RR  =  3.98; 95%  CI, 2.01–7.87) 

(Vinnikov et  al. 2008; West et  al. 2011), as reviewed by 

Cahill and colleagues (2016), but the quality of evidence 

from the reviewed trials was low, in part because of small 

sample sizes and loss to follow-up. Furthermore, the absolute sustained long-term quit rates were modest (8.5% for 

cytisine vs. 2.1% for placebo at 1 year), which is generally 

consistent with cessation rates in the United States (Babb 

et al. 2017; Wang et al. 2019). The modest sustained quit 

rates were attributed to the minimal behavioral support 

provided and to the study locations, which included countries with more limited tobacco control policies than the 

United States. In an open-label, randomized comparative 

effectiveness trial conducted in New Zealand, Walker and 

colleagues (2014) reported 22% sustained abstinence for 

cytisine at the 6-month follow-up compared with 15% for 

the nicotine patch (RR = 1.4; 95% CI, 1.1–1.8).

The reported side effects of cytisine are primarily gastrointestinal, including abdominal discomfort, dry mouth, 

dyspepsia, and nausea. Notably, the cost of cytisine in places 

where it is available has increased, but it is still one-half to 

one-twentieth the cost of other cessation medications. 

In February 2019, the FDA Center for Drug 

Evaluation and Research (2019) issued a draft version of 

guidance intended to assist sponsors in the clinical development of NRT drug products, including but not limited to 

products intended to help cigarette smokers stop smoking. 

This guidance incorporates feedback received from an 

FDA public hearing in January 2018 and from a notice in 

the Federal Register in November 2017 requesting comments on the FDA’s approach to evaluating the safety and 

effectiveness of NRT products, including how these products should be used and labeled (Federal Register 2017; 

FDA 2019a). 

Summary of the Evidence

The prevalence of cigarette smoking in the general U.S. population has declined steadily since the 1960s 

(USDHHS 2014), due in part to the development and concerted implementation of evidence-based tobacco control 

interventions, including cessation interventions. Since 

2002 the number of former smokers has been greater than 

the number of current smokers (CDC 2005). However, as 

of 2017, there were still 34  million adult current cigarette smokers in the United States (Wang et al. 2018). This 

chapter highlighted key topics and developments associated with the content and delivery of smoking cessation 

interventions, with a focus on emerging evidence that can 

inform future smoking cessation efforts. 

The evidence indicates that nicotine addiction is a 

chronic, relapsing disorder and that the chances of successfully sustaining a quit attempt and avoiding relapse 

increase with the use of evidence-based cessation treatments, with those chances generally increasing with 

higher dose, duration, and intensity of treatment. A large 

number of high-quality studies continues to support 

the use of behavioral counseling, pharmacologic interventions, and combined counseling and pharmacologic 

interventions for smoking cessation, with the latter combination being the most effective approach. Effective counseling interventions include diverse behavioral treatments 

that can be delivered effectively in a variety of formats, 

including individual, group, and telephone counseling. 

There are currently seven FDA-approved medications for 

use as first-line tobacco cessation treatments. Although 

the products are not approved for combination use, there 

is clear scientific evidence that combinations of shortand long-acting forms of NRT are more effective in promoting cessation than individual forms of NRT (Lindson 

et al. 2019). Both behavioral and pharmacologic tobacco 

cessation treatments have been shown to be highly costeffective (see Chapter 5).

Nationally representative data indicate that about 

three in five U.S. adults who ever smoked have quit successfully and that just over half of current smokers try to 

quit each year, but the success of any given quit attempt 

remains low (Babb et al. 2017). Despite progress over the 

past 30 years, the reach and use of smoking cessation interventions remain low, with less than one-third of smokers 

using any proven cessation treatments (counseling 

and/or medication) from 2000 to 2015 (Babb et al. 2017). 

Regardless of the generally wide availability of proven cessation treatments, about two-thirds of smokers still attempt 

to quit without using these treatments, contributing to 

low rates of success (Hughes et al. 2004; Fiore et al. 2008).

Increasing smoking cessation will require several 

strategies, including (1) increasing the appeal, reach, and 

use of existing evidence-based cessation interventions; 

(2) further increasing the effectiveness of those interventions; and (3)  developing additional cessation interventions that have greater reach and/or effectiveness than 

existing interventions or that appeal to and are used by 

different populations of smokers. Increasing cessation 

at the population level will also require increasing quit 
Interventions for Smoking Cessation and Treatments for Nicotine Dependence 547

Smoking Cessation

attempts (including the number of smokers making quit 

attempts and the number of quit attempts that individual 

smokers make) and quit success, with quit attempts being 

driven primarily by the reach of cessation interventions 

and quit success being driven primarily by the intensity of 

these interventions (Zhu et al. 2012).

Additional research is needed to better understand (a)  how e-cigarette use impacts smoking cessation, including determining which types of e-cigarettes 

and which patterns and contexts of e-cigarette use may 

facilitate or hinder smoking cessation among adults, and 

(b) the negative impacts of e-cigarette use (e.g., increases 

in youth initiation of e-cigarettes, conventional cigarettes, 

and other tobacco products; dual use of e-cigarettes and 

other combusted tobacco products; decreased use of 

evidence-based cessation treatments; and decreased or 

delayed complete cessation of conventional cigarettes and 

other combustible tobacco products). The research will 

need to track the changes in products over time.

Promising directions include leveraging emerging 

technologies to enhance the sustained engagement of 

smokers in cessation treatment, accelerating the integration of cessation services across multiple platforms and 

within healthcare systems, and developing new tobacco 

cessation medications and new indications for existing cessation medications. Although this chapter focuses on cessation interventions at the individual level, several population- and policy-based approaches (discussed in Chapter 7) 

have also been found to be effective in increasing tobacco 

cessation. Many of these broader approaches can be leveraged to complement and further increase the use of the 

cessation treatments described in this chapter.

Conclusions

1. The evidence is sufficient to infer that behavioral 

counseling and cessation medication interventions 

increase smoking cessation compared with self-help 

materials or no treatment. 

2. The evidence is sufficient to infer that behavioral 

counseling and cessation medications are independently effective in increasing smoking cessation, 

and even more effective when used in combination.

3. The evidence is sufficient to infer that proactive quitline counseling, when provided alone or in combination with cessation medications, increases smoking 

cessation.

4. The evidence is sufficient to infer that short text 

message services about cessation are independently 

effective in increasing smoking cessation, particularly if they are interactive or tailored to individual 

text responses.

5. The evidence is sufficient to infer that web or Internetbased interventions increase smoking cessation and 

can be more effective when they contain behavior 

change techniques and interactive components.

6. The evidence is inadequate to infer that smartphone 

apps for smoking cessation are independently effective in increasing smoking cessation.

7. The evidence is sufficient to infer that combining 

short- and long-acting forms of nicotine replacement 

therapy increases smoking cessation compared with 

using single forms of nicotine replacement therapy.

8. The evidence is suggestive but not sufficient to infer 

that pre-loading (e.g.,  initiating cessation medication in advance of a quit attempt), especially with 

the nicotine patch, can increase smoking cessation.

9. The evidence is suggestive but not sufficient to infer 

that very-low-nicotine-content cigarettes can reduce 

smoking and nicotine dependence and increase 

smoking cessation when full-nicotine cigarettes are 

readily available; the effects on cessation may be further strengthened in an environment in which conventional cigarettes and other combustible tobacco 

products are not readily available.

10. The evidence is inadequate to infer that e-cigarettes, 

in general, increase smoking cessation. However, 

the evidence is suggestive but not sufficient to infer 

that the use of e-cigarettes containing nicotine is 

associated with increased smoking cessation compared with the use of e-cigarettes not containing 

nicotine, and the evidence is suggestive but not sufficient to infer that more frequent use of e-cigarettes 

is associated with increased smoking cessation compared with less frequent use of e-cigarettes.

11. The evidence is sufficient to infer that certain life 

events—including hospitalization, surgery, and 

lung cancer screening—can trigger attempts to quit 
A Report of the Surgeon General

548 Chapter 6

smoking, uptake of smoking cessation treatment, 

and smoking cessation.

12. The evidence is suggestive but not sufficient to infer 

that fully and consistently integrating standardized, 

evidence-based smoking cessation interventions 

into lung cancer screening increases smoking cessation while avoiding potential adverse effects of this 

screening on cessation outcomes.

13. The evidence is suggestive but not sufficient to infer 

that cytisine increases smoking cessation.
Interventions for Smoking Cessation and Treatments for Nicotine Dependence 549

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